{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:04:33Z","timestamp":1793898273953,"version":"4.8.0"},"reference-count":210,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Rheumatol"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1038\/s41584-026-01365-7","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T15:36:15Z","timestamp":1775576175000},"page":"285-301","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus"],"prefix":"10.1038","volume":"22","author":[{"given":"Danni Yi-Dan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-7371","authenticated-orcid":false,"given":"Carlos","family":"Castrillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-2055","authenticated-orcid":false,"given":"Elliot","family":"Akama-Garren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"1365_CR1","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.cell.2017.07.026","volume":"170","author":"SE Degn","year":"2017","unstructured":"Degn, S. E. et al. Clonal evolution of autoreactive germinal centers. Cell 170, 913\u2013926.e19 (2017).","journal-title":"Cell"},{"key":"1365_CR2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/sciimmunol.adi8150","volume":"9","author":"T van den Broek","year":"2024","unstructured":"van den Broek, T. et al. Invasion of spontaneous germinal centers by naive B cells is rapid and persistent. Sci. Immunol. 9, 1\u201311 (2024).","journal-title":"Sci. Immunol."},{"key":"1365_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00427","volume":"9","author":"S Malkiel","year":"2018","unstructured":"Malkiel, S., Barlev, A. N., Atisha-Fregoso, Y., Suurmond, J. & Diamond, B. Plasma cell differentiation pathways in systemic lupus erythematosus. Front. Immunol. 9, 427 (2018).","journal-title":"Front. Immunol."},{"key":"1365_CR4","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/imr.12741","volume":"288","author":"SA Jenks","year":"2019","unstructured":"Jenks, S. A., Cashman, K. S., Woodruff, M. C., Lee, F. E. H. & Sanz, I. Extrafollicular responses in humans and SLE. Immunol. Rev. 288, 136\u2013148 (2019).","journal-title":"Immunol. Rev."},{"key":"1365_CR5","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1002\/(SICI)1521-4141(199904)29:04<1314::AID-IMMU1314>3.0.CO;2-4","volume":"29","author":"C Garc\u00eda De Vinuesa","year":"1999","unstructured":"Garc\u00eda De Vinuesa, C., O\u2019Leary, P., Sze, D. M. Y., Toellner, K. M. & MacLennan, I. C. M. T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci. Eur. J. Immunol. 29, 1314\u20131323 (1999).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR6","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1056\/NEJMoa021933","volume":"349","author":"MR Arbuckle","year":"2003","unstructured":"Arbuckle, M. R. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526\u20131533 (2003).","journal-title":"N. Engl. J. Med."},{"key":"1365_CR7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.imlet.2014.11.001","volume":"163","author":"C Cornaby","year":"2015","unstructured":"Cornaby, C. et al. B cell epitope spreading: mechanisms and contribution to autoimmune diseases. Immunol. Lett. 163, 56\u201368 (2015).","journal-title":"Immunol. Lett."},{"key":"1365_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42541-7","volume":"14","author":"C Fahlquist-Hagert","year":"2023","unstructured":"Fahlquist-Hagert, C. et al. Antigen presentation by B cells enables epitope spreading across an MHC barrier. Nat. Commun. 14, 6941 (2023).","journal-title":"Nat. Commun."},{"key":"1365_CR9","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.immuni.2018.08.015","volume":"49","author":"SA Jenks","year":"2018","unstructured":"Jenks, S. A. et al. Distinct effector b cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity 49, 725\u2013739.e6 (2018).","journal-title":"Immunity"},{"key":"1365_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2022.1021370","volume":"13","author":"LF Voss","year":"2022","unstructured":"Voss, L. F. et al. The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus. Front. Immunol. 13, 1\u201319 (2022).","journal-title":"Front. Immunol."},{"key":"1365_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ads8226","volume":"10","author":"DY Zhu","year":"2025","unstructured":"Zhu, D. Y. et al. CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model. Sci. Immunol. 10, eads8226 (2025).","journal-title":"Sci. Immunol."},{"key":"1365_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1208282","volume":"14","author":"RM Baxter","year":"2023","unstructured":"Baxter, R. M. et al. Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus. Front. Immunol. 14, 1208282 (2023).","journal-title":"Front. Immunol."},{"key":"1365_CR13","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1126\/science.1086907","volume":"301","author":"H Wardemann","year":"2003","unstructured":"Wardemann, H. et al. Predominant autoantibody production by early human B cell precursors. Science 301, 1374\u20131377 (2003).","journal-title":"Science"},{"key":"1365_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.2011.06347.x","volume":"1246","author":"E Meffre","year":"2011","unstructured":"Meffre, E. The establishment of early B cell tolerance in humans: lessons from primary immunodeficiency diseases. Ann. N. Y. Acad. Sci. 1246, 1\u201310 (2011).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"1365_CR15","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.4049\/jimmunol.172.10.5967","volume":"172","author":"NA Danke","year":"2004","unstructured":"Danke, N. A., Koelle, D. M., Yee, C., Beheray, S. & Kwok, W. W. Autoreactive T cells in healthy individuals. J. Immunol. 172, 5967\u20135972 (2004).","journal-title":"J. Immunol."},{"key":"1365_CR16","first-page":"487","volume":"24","author":"V Lee","year":"2023","unstructured":"Lee, V. et al. The endogenous repertoire harbors self-reactive CD4+ T cell clones that adopt a follicular helper T cell-like phenotype at steady state. Nat. Immunol. 24, 487\u2013500 (2023).","journal-title":"Nat. Immunol."},{"key":"1365_CR17","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adj7029","volume":"9","author":"EH Akama-Garren","year":"2024","unstructured":"Akama-Garren, E. H. et al. T cell help shapes B cell tolerance. Sci. Immunol. 9, eadj7029 (2024).","journal-title":"Sci. Immunol."},{"key":"1365_CR18","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/imr.12820","volume":"292","author":"KS Cashman","year":"2019","unstructured":"Cashman, K. S. et al. Understanding and measuring human B-cell tolerance and its breakdown in autoimmune disease. Immunol. Rev. 292, 76\u201389 (2019).","journal-title":"Immunol. Rev."},{"key":"1365_CR19","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/nri.2017.19","volume":"17","author":"D Nemazee","year":"2017","unstructured":"Nemazee, D. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol. 17, 281\u2013294 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"1365_CR20","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/337562a0","volume":"337","author":"DA Nemazee","year":"1989","unstructured":"Nemazee, D. A. & Biirki, K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature 337, 562\u2013566 (1989).","journal-title":"Nature"},{"key":"1365_CR21","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/imr.12818","volume":"292","author":"C Tan","year":"2019","unstructured":"Tan, C., Noviski, M., Huizar, J. & Zikherman, J. Self-reactivity on a spectrum: a sliding scale of peripheral B cell tolerance. Immunol. Rev. 292, 37\u201360 (2019).","journal-title":"Immunol. Rev."},{"key":"1365_CR22","doi-asserted-by":"publisher","unstructured":"Fischer, A. A., Corcoran, M., Brouwer, P. J. M. & Chernyshev, M. Isolation of genetically diverse influenza antibodies highlights the role of IG germline gene variation and informs the design of population- comprehensive vaccine strategies. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.07.04.663145 (2025).","DOI":"10.1101\/2025.07.04.663145"},{"key":"1365_CR23","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.immuni.2022.07.006","volume":"55","author":"M Sangesland","year":"2022","unstructured":"Sangesland, M. et al. Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus. Immunity 55, 1693\u20131709.e8 (2022).","journal-title":"Immunity"},{"key":"1365_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-40070-x","volume":"14","author":"OL Rodriguez","year":"2023","unstructured":"Rodriguez, O. L. et al. Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire. Nat. Commun. 14, 1\u201318 (2023).","journal-title":"Nat. Commun."},{"key":"1365_CR25","doi-asserted-by":"publisher","first-page":"4926","DOI":"10.4049\/jimmunol.1202263","volume":"191","author":"C Richardson","year":"2013","unstructured":"Richardson, C. et al. Molecular basis of 9G4 B cell autoreactivity in human systemic lupus erythematosus. J. Immunol. 191, 4926\u20134939 (2013).","journal-title":"J. Immunol."},{"key":"1365_CR26","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/ni.3175","volume":"16","author":"CM Tipton","year":"2015","unstructured":"Tipton, C. M. et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat. Immunol. 16, 755\u2013765 (2015).","journal-title":"Nat. Immunol."},{"key":"1365_CR27","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1136\/ard.57.9.566","volume":"57","author":"DA Isenberg","year":"1998","unstructured":"Isenberg, D. A. et al. Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus. Ann. Rheum. Dis. 57, 566\u2013570 (1998).","journal-title":"Ann. Rheum. Dis."},{"key":"1365_CR28","doi-asserted-by":"publisher","first-page":"5425","DOI":"10.1182\/blood-2010-10-312942","volume":"117","author":"ED Charles","year":"2011","unstructured":"Charles, E. D. et al. Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset. Blood 117, 5425\u20135437 (2011).","journal-title":"Blood"},{"key":"1365_CR29","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1182\/blood-2011-05-353821","volume":"118","author":"M Visentini","year":"2011","unstructured":"Visentini, M. et al. The VH1-69-expressing marginal zone B cells expanded in HCV-associated mixed cryoglobulinemia display proliferative anergy irrespective of CD21low phenotype. Blood 118, 3440\u20133441 (2011).","journal-title":"Blood"},{"key":"1365_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.81012","volume":"12","author":"C Castrillon","year":"2023","unstructured":"Castrillon, C. et al. Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers. eLife 12, 1\u201321 (2023).","journal-title":"eLife"},{"key":"1365_CR31","doi-asserted-by":"publisher","first-page":"5486","DOI":"10.1016\/j.cell.2023.10.022","volume":"186","author":"A Sprumont","year":"2023","unstructured":"Sprumont, A., Rodrigues, A., McGowan, S. J., Bannard, C. & Bannard, O. Germinal centers output clonally diverse plasma cell populations expressing high- and low-affinity antibodies. Cell 186, 5486\u20135499.e13 (2023).","journal-title":"Cell"},{"key":"1365_CR32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.immuni.2023.12.010","volume":"57","author":"HJ Sutton","year":"2024","unstructured":"Sutton, H. J. et al. Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation. Immunity 57, 245\u2013255.e5 (2024).","journal-title":"Immunity"},{"key":"1365_CR33","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/nature05573","volume":"446","author":"TA Schwickert","year":"2007","unstructured":"Schwickert, T. A. et al. In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446, 83\u201387 (2007).","journal-title":"Nature"},{"key":"1365_CR34","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.it.2024.03.002","volume":"45","author":"R Tach\u00f3-Pi\u00f1ot","year":"2024","unstructured":"Tach\u00f3-Pi\u00f1ot, R. & Vinuesa, C. G. Affinity-independent plasma cell differentiation in germinal centers. Trends Immunol. 45, 234\u2013236 (2024).","journal-title":"Trends Immunol."},{"key":"1365_CR35","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1172\/JCI24179","volume":"115","author":"A Cappione","year":"2005","unstructured":"Cappione, A. et al. Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J. Clin. Invest. 115, 3205\u20133216 (2005).","journal-title":"J. Clin. Invest."},{"key":"1365_CR36","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.immuni.2012.07.017","volume":"37","author":"TD Chan","year":"2012","unstructured":"Chan, T. D. et al. Elimination of germinal-center-derived self-reactive b cells is governed by the location and concentration of self-antigen. Immunity 37, 893\u2013904 (2012).","journal-title":"Immunity"},{"key":"1365_CR37","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.immuni.2006.07.014","volume":"25","author":"R Berland","year":"2006","unstructured":"Berland, R. et al. Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice. Immunity 25, 429\u2013440 (2006).","journal-title":"Immunity"},{"key":"1365_CR38","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1016\/j.celrep.2019.10.086","volume":"29","author":"CE van der Poel","year":"2019","unstructured":"van der Poel, C. E. et al. Follicular dendritic cells modulate germinal center B cell diversity through Fc\u03b3RIIB. Cell Rep. 29, 2745\u20132755.e4 (2019).","journal-title":"Cell Rep."},{"key":"1365_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114978","volume":"43","author":"GM Sanchez","year":"2024","unstructured":"Sanchez, G. M. et al. Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus. Cell Rep. 43, 114978 (2024).","journal-title":"Cell Rep."},{"key":"1365_CR40","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.4049\/jimmunol.0901690","volume":"183","author":"TD Chan","year":"2009","unstructured":"Chan, T. D. et al. Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J. Immunol. 183, 3139\u20133149 (2009).","journal-title":"J. Immunol."},{"key":"1365_CR41","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1034\/j.1600-065X.2003.00058.x","volume":"194","author":"ICM MacLennan","year":"2003","unstructured":"MacLennan, I. C. M. et al. Extrafollicular antibody responses. Immunol. Rev. 194, 8\u201318 (2003).","journal-title":"Immunol. Rev."},{"key":"1365_CR42","doi-asserted-by":"publisher","first-page":"3339","DOI":"10.1002\/eji.200737752","volume":"37","author":"RA Herlands","year":"2007","unstructured":"Herlands, R. A., William, J., Hershberg, U. & Shlomchik, M. J. Anti-chromatin antibodies drive in vivo antigen-specific activation and somatic hypermutation of rheumatoid factor B cells at extrafollicular sites. Eur. J. Immunol. 37, 3339\u20133351 (2007).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR43","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1002\/eji.201041354","volume":"41","author":"Z Liu","year":"2011","unstructured":"Liu, Z., Zou, Y. R. & Davidson, A. Plasma cells in systemic lupus erythematosus: the long and short of it all. Eur. J. Immunol. 41, 588\u2013591 (2011).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/imr.70066","volume":"336","author":"N Baumgarth","year":"2025","unstructured":"Baumgarth, N. Extrafollicular B cell responses \u2014 is one tent big enough? Immunol. Rev. 336, 1\u20139 (2025).","journal-title":"Immunol. Rev."},{"key":"1365_CR45","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1016\/j.immuni.2025.08.007","volume":"58","author":"SC Eisenbarth","year":"2025","unstructured":"Eisenbarth, S. C. et al. A roadmap for defining \u201cextrafollicular\u201d B cell responses. Immunity 58, 2627\u20132645 (2025).","journal-title":"Immunity"},{"key":"1365_CR46","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S1074-7613(02)00389-8","volume":"17","author":"M Bal\u00e1zs","year":"2002","unstructured":"Bal\u00e1zs, M., Martin, F., Zhou, T. & Kearney, J. F. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity 17, 341\u2013352 (2002).","journal-title":"Immunity"},{"key":"1365_CR47","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/S1074-7613(01)00129-7","volume":"14","author":"F Martin","year":"2001","unstructured":"Martin, F., Oliver, A. M. & Kearney, J. F. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617\u2013629 (2001).","journal-title":"Immunity"},{"key":"1365_CR48","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abm9060","volume":"7","author":"JHY Siu","year":"2022","unstructured":"Siu, J. H. Y. et al. Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood. Sci. Immunol. 7, eabm9060 (2022).","journal-title":"Sci. Immunol."},{"key":"1365_CR49","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1084\/jem.20042251","volume":"201","author":"S Yurasov","year":"2005","unstructured":"Yurasov, S. et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J. Exp. Med. 201, 703\u2013711 (2005).","journal-title":"J. Exp. Med."},{"key":"1365_CR50","doi-asserted-by":"publisher","first-page":"6624","DOI":"10.4049\/jimmunol.178.10.6624","volume":"178","author":"C Wei","year":"2007","unstructured":"Wei, C. et al. A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J. Immunol. 178, 6624\u20136633 (2007).","journal-title":"J. Immunol."},{"key":"1365_CR51","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.4049\/jimmunol.0901297","volume":"183","author":"GE Weiss","year":"2009","unstructured":"Weiss, G. E. et al. Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J. Immunol. 183, 2176\u20132182 (2009).","journal-title":"J. Immunol."},{"key":"1365_CR52","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1182\/blood-2011-01-330530","volume":"118","author":"Y Hao","year":"2011","unstructured":"Hao, Y., O\u2019Neill, P., Naradikian, M. S., Scholz, J. L. & Cancro, M. P. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118, 1294\u20131304 (2011).","journal-title":"Blood"},{"key":"1365_CR53","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1182\/blood-2011-01-331462","volume":"118","author":"AV Rubtsov","year":"2011","unstructured":"Rubtsov, A. V. et al. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood 118, 1305\u20131315 (2011).","journal-title":"Blood"},{"key":"1365_CR54","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adj4748","volume":"4748","author":"X Gao","year":"2024","unstructured":"Gao, X. et al. Zeb2 drives the formation of CD11c+ atypical B cells to sustain germinal centers that control persistent infection. Sci. Immunol. 4748, eadj4748 (2024).","journal-title":"Sci. Immunol."},{"key":"1365_CR55","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/s41423-020-00542-2","volume":"17","author":"B Oliviero","year":"2020","unstructured":"Oliviero, B. et al. Expansion of atypical memory B cells is a prominent feature of COVID-19. Cell. Mol. Immunol. 17, 1101\u20131103 (2020).","journal-title":"Cell. Mol. Immunol."},{"key":"1365_CR56","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.coi.2003.09.016","volume":"15","author":"ML Fields","year":"2003","unstructured":"Fields, M. L. & Erikson, J. The regulation of lupus-associated autoantibodies: Immunoglobulin transgenic models. Curr. Opin. Immunol. 15, 709\u2013717 (2003).","journal-title":"Curr. Opin. Immunol."},{"key":"1365_CR57","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.immuni.2007.12.004","volume":"28","author":"MJ Shlomchik","year":"2008","unstructured":"Shlomchik, M. J. Sites and stages of autoreactive B cell activation and regulation. Immunity 28, 18\u201328 (2008).","journal-title":"Immunity"},{"key":"1365_CR58","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1084\/jem.20060087","volume":"203","author":"D Paus","year":"2006","unstructured":"Paus, D. et al. Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation. J. Exp. Med. 203, 1081\u20131091 (2006).","journal-title":"J. Exp. Med."},{"key":"1365_CR59","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/334676a0","volume":"334","author":"CC Goodnow","year":"1988","unstructured":"Goodnow, C. C. et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334, 676\u2013682 (1988).","journal-title":"Nature"},{"key":"1365_CR60","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1084\/jem.20050630","volume":"202","author":"CM Lau","year":"2005","unstructured":"Lau, C. M. et al. RNA-associated autoantigens activate B cells by combined B cell antigen receptor\/Toll-like receptor 7 engagement. J. Exp. Med. 202, 1171\u20131177 (2005).","journal-title":"J. Exp. Med."},{"key":"1365_CR61","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S1074-7613(03)00323-6","volume":"19","author":"GA Viglianti","year":"2003","unstructured":"Viglianti, G. A. et al. Activation of autoreactive B cells by CpG dsDNA. Immunity 19, 837\u2013847 (2003).","journal-title":"Immunity"},{"key":"1365_CR62","doi-asserted-by":"publisher","first-page":"5875","DOI":"10.4049\/jimmunol.181.9.5875","volume":"181","author":"MB Uccellini","year":"2008","unstructured":"Uccellini, M. B. et al. Autoreactive B cells discriminate CpG-rich and CpG-poor DNA and this response is modulated by IFN-\u03b1. J. Immunol. 181, 5875\u20135884 (2008).","journal-title":"J. Immunol."},{"key":"1365_CR63","doi-asserted-by":"publisher","first-page":"7932","DOI":"10.1073\/pnas.1018571108","volume":"108","author":"RA Sweet","year":"2011","unstructured":"Sweet, R. A. et al. Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo. Proc. Natl Acad. Sci. USA 108, 7932\u20137937 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR64","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.immuni.2008.06.009","volume":"29","author":"RA Herlands","year":"2008","unstructured":"Herlands, R. A., Christensen, S. R., Sweet, R. A., Hershberg, U. & Shlomchik, M. J. T cell-independent and Toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29, 249\u2013260 (2008).","journal-title":"Immunity"},{"key":"1365_CR65","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81012","volume":"12","author":"C Castrillon","year":"2022","unstructured":"Castrillon, C. et al. Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers. eLife 12, e81012 (2022).","journal-title":"eLife"},{"key":"1365_CR66","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.immuni.2020.11.006","volume":"53","author":"RA Elsner","year":"2020","unstructured":"Elsner, R. A. & Shlomchik, M. J. Germinal center and extrafollicular B cell responses in vaccination, immunity, and autoimmunity. Immunity 53, 1136\u20131150 (2020).","journal-title":"Immunity"},{"key":"1365_CR67","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/bs.ai.2024.02.002","volume":"162","author":"Y He","year":"2024","unstructured":"He, Y. & Vinuesa, C. G. Germinal center versus extrafollicular responses in systemic autoimmunity: who turns the blade on self? Adv. Immunol. 162, 109\u2013133 (2024).","journal-title":"Adv. Immunol."},{"key":"1365_CR68","doi-asserted-by":"publisher","DOI":"10.1111\/imr.70004","volume":"330","author":"J Staniek","year":"2025","unstructured":"Staniek, J. & Rizzi, M. Signaling activation and modulation in extrafollicular B cell responses. Immunol. Rev. 330, e70004 (2025).","journal-title":"Immunol. Rev."},{"key":"1365_CR69","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jim.2010.12.008","volume":"365","author":"X He","year":"2011","unstructured":"He, X. et al. Plasmablast-derived polyclonal antibody response after influenza vaccination. J. Immunol. Methods 365, 67\u201375 (2011).","journal-title":"J. Immunol. Methods"},{"key":"1365_CR70","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jim.2008.09.025","volume":"340","author":"SY Kyu","year":"2009","unstructured":"Kyu, S. Y. et al. Frequencies of human influenza-specific antibody secreting cells or plasmablasts post vaccination from fresh and frozen peripheral blood mononuclear cells. J. Immunol. Methods 340, 42\u201347 (2009).","journal-title":"J. Immunol. Methods"},{"key":"1365_CR71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-17798-x","volume":"11","author":"CD Scharer","year":"2020","unstructured":"Scharer, C. D. et al. Antibody-secreting cell destiny emerges during the initial stages of B-cell activation. Nat. Commun. 11, 1\u201314 (2020).","journal-title":"Nat. Commun."},{"key":"1365_CR72","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1016\/j.immuni.2021.08.017","volume":"54","author":"V Glaros","year":"2021","unstructured":"Glaros, V. et al. Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response. Immunity 54, 2005\u20132023.e10 (2021).","journal-title":"Immunity"},{"key":"1365_CR73","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn8934","volume":"379","author":"A Aung","year":"2023","unstructured":"Aung, A. et al. Low protease activity in B cell follicles promotes retention of intact antigens after immunization. Science 379, eabn8934 (2023).","journal-title":"Science"},{"key":"1365_CR74","doi-asserted-by":"publisher","first-page":"171","DOI":"10.4049\/jimmunol.2300500","volume":"212","author":"A Aung","year":"2024","unstructured":"Aung, A. & Irvine, D. J. Modulating antigen availability in lymphoid organs to shape the humoral immune response to vaccines. J. Immunol. 212, 171\u2013178 (2024).","journal-title":"J. Immunol."},{"key":"1365_CR75","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1126\/science.adf8531","volume":"383","author":"D Dai","year":"2024","unstructured":"Dai, D. et al. The transcription factor ZEB2 drives the formation of age-associated B cells. Science 383, 413\u2013421 (2024).","journal-title":"Science"},{"key":"1365_CR76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/sciimmunol.adk1643","volume":"9","author":"M Goto","year":"2024","unstructured":"Goto, M. et al. Age-associated CD4+ T cells with B cell\u2013promoting functions are regulated by ZEB2 in autoimmunity. Sci. Immunol. 9, 1\u201316 (2024).","journal-title":"Sci. Immunol."},{"key":"1365_CR77","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41565-020-00790-3","volume":"16","author":"A Singh","year":"2021","unstructured":"Singh, A. Eliciting B cell immunity against infectious diseases using nanovaccines. Nat. Nanotechnol. 16, 16\u201324 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"1365_CR78","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.immuni.2013.02.023","volume":"38","author":"BA Heesters","year":"2013","unstructured":"Heesters, B. A. et al. Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity 38, 1164\u20131175 (2013).","journal-title":"Immunity"},{"key":"1365_CR79","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/76032","volume":"25","author":"M Napirei","year":"2000","unstructured":"Napirei, M. et al. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat. Genet. 25, 177\u2013181 (2000).","journal-title":"Nat. Genet."},{"key":"1365_CR80","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/ng.975","volume":"43","author":"SM Al-Mayouf","year":"2011","unstructured":"Al-Mayouf, S. M. et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat. Genet. 43, 1186\u20131188 (2011).","journal-title":"Nat. Genet."},{"key":"1365_CR81","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/eji.201847875","volume":"49","author":"EF Kenny","year":"2019","unstructured":"Kenny, E. F., Raupach, B., Abu Abed, U., Brinkmann, V. & Zychlinsky, A. Dnase1-deficient mice spontaneously develop a systemic lupus erythematosus-like disease. Eur. J. Immunol. 49, 590\u2013599 (2019).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR82","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.immuni.2020.04.015","volume":"52","author":"C Soni","year":"2020","unstructured":"Soni, C. et al. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. Immunity 52, 1022\u20131038.e7 (2020).","journal-title":"Immunity"},{"key":"1365_CR83","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/S1074-7613(00)80669-X","volume":"9","author":"AP Prodeus","year":"1998","unstructured":"Prodeus, A. P. et al. A critical role for complement in maintenance of self-tolerance. Immunity 9, 721\u2013731 (1998).","journal-title":"Immunity"},{"key":"1365_CR84","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1600-065X.2007.00556.x","volume":"219","author":"R Roozendaal","year":"2007","unstructured":"Roozendaal, R. & Carroll, M. C. Complement receptors CD21 and CD35 in humoral immunity. Immunol. Rev. 219, 157\u2013166 (2007).","journal-title":"Immunol. Rev."},{"key":"1365_CR85","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.molimm.2004.03.017","volume":"41","author":"MC Carroll","year":"2004","unstructured":"Carroll, M. C. The complement system in B cell regulation. Mol. Immunol. 41, 141\u2013146 (2004).","journal-title":"Mol. Immunol."},{"key":"1365_CR86","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.4049\/jimmunol.168.3.1036","volume":"168","author":"S Einav","year":"2002","unstructured":"Einav, S., Pozdnyakova, O. O., Ma, M. & Carroll, M. C. Complement C4 Is protective for lupus disease independent of C31. J. Immunol. 168, 1036\u20131041 (2002).","journal-title":"J. Immunol."},{"key":"1365_CR87","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1002\/1521-4141(200209)32:9<2672::AID-IMMU2672>3.0.CO;2-X","volume":"32","author":"E Paul","year":"2002","unstructured":"Paul, E., Pozdnyakova, O. O., Mitchell, E. & Carroll, M. C. Anti-DNA autoreactivity in C4-deficient mice. Eur. J. Immunol. 32, 2672\u20132679 (2002).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR88","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1002\/eji.201343412","volume":"43","author":"P Chatterjee","year":"2013","unstructured":"Chatterjee, P. et al. Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner. Eur. J. Immunol. 43, 2441\u20132450 (2013).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR89","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108330","volume":"33","author":"L Simoni","year":"2020","unstructured":"Simoni, L. et al. Complement C4A regulates autoreactive B cells in murine lupus. Cell Rep. 33, 108330 (2020).","journal-title":"Cell Rep."},{"key":"1365_CR90","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1084\/jem.192.10.1425","volume":"192","author":"JE Gretz","year":"2000","unstructured":"Gretz, J. E., Norbury, C. C., Anderson, A. O., Proudfoot, A. E. I. & Shaw, S. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J. Exp. Med. 192, 1425\u20131440 (2000).","journal-title":"J. Exp. Med."},{"key":"1365_CR91","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2004.11.013","volume":"22","author":"M Sixt","year":"2005","unstructured":"Sixt, M. et al. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22, 19\u201329 (2005).","journal-title":"Immunity"},{"key":"1365_CR92","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.immuni.2008.12.014","volume":"30","author":"R Roozendaal","year":"2009","unstructured":"Roozendaal, R. et al. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30, 264\u2013276 (2009).","journal-title":"Immunity"},{"key":"1365_CR93","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1016\/j.celrep.2019.10.069","volume":"29","author":"RA Elsner","year":"2019","unstructured":"Elsner, R. A. & Shlomchik, M. J. IL-12 blocks Tfh cell differentiation during Salmonella infection, thereby contributing to germinal center suppression. Cell Rep. 29, 2796\u20132809.e5 (2019).","journal-title":"Cell Rep."},{"key":"1365_CR94","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.immuni.2022.01.013","volume":"55","author":"A Biram","year":"2022","unstructured":"Biram, A. et al. Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired metabolic adaptation. Immunity 55, 442\u2013458.e8 (2022).","journal-title":"Immunity"},{"key":"1365_CR95","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41590-024-01858-1","volume":"25","author":"RA Elsner","year":"2024","unstructured":"Elsner, R. A., Smita, S. & Shlomchik, M. J. IL-12 induces a B cell-intrinsic IL-12\/IFN\u03b3 feed-forward loop promoting extrafollicular B cell responses. Nat. Immunol. 25, 1283\u20131295 (2024).","journal-title":"Nat. Immunol."},{"key":"1365_CR96","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1136\/annrheumdis-2015-208140","volume":"75","author":"ME Munroe","year":"2016","unstructured":"Munroe, M. E. et al. Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann. Rheum. Dis. 75, 2014\u20132021 (2016).","journal-title":"Ann. Rheum. Dis."},{"key":"1365_CR97","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1016\/j.celrep.2019.04.019","volume":"27","author":"CC Kim","year":"2019","unstructured":"Kim, C. C., Baccarella, A. M., Bayat, A., Pepper, M. & Fontana, M. F. FCRL5+ memory B cells exhibit robust recall responses. Cell Rep. 27, 1446\u20131460.e4 (2019).","journal-title":"Cell Rep."},{"key":"1365_CR98","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.07218","volume":"4","author":"S Portugal","year":"2015","unstructured":"Portugal, S. et al. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. eLife 4, 1\u201321 (2015).","journal-title":"eLife"},{"key":"1365_CR99","doi-asserted-by":"publisher","first-page":"2772","DOI":"10.1016\/j.immuni.2024.11.006","volume":"57","author":"CE Faliti","year":"2024","unstructured":"Faliti, C. E. et al. Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis. Immunity 57, 2772\u20132789.e8 (2024).","journal-title":"Immunity"},{"key":"1365_CR100","doi-asserted-by":"publisher","first-page":"115190","DOI":"10.1016\/j.celrep.2024.115190","volume":"44","author":"Y Kim","year":"2025","unstructured":"Kim, Y. et al. IL-21 shapes the B cell response in a context-dependent manner. Cell Rep. 44, 115190 (2025).","journal-title":"Cell Rep."},{"key":"1365_CR101","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41591-018-0254-9","volume":"25","author":"S Caielli","year":"2019","unstructured":"Caielli, S. et al. A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate. Nat. Med. 25, 75\u201381 (2019).","journal-title":"Nat. Med."},{"key":"1365_CR102","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41581-023-00732-x","volume":"19","author":"CG Vinuesa","year":"2023","unstructured":"Vinuesa, C. G., Shen, N. & Ware, T. Genetics of SLE: mechanistic insights from monogenic disease and disease-associated variants. Nat. Rev. Nephrol. 19, 558\u2013572 (2023).","journal-title":"Nat. Rev. Nephrol."},{"key":"1365_CR103","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/s41590-019-0419-9","volume":"20","author":"CD Scharer","year":"2019","unstructured":"Scharer, C. D. et al. Epigenetic programming underpins B cell dysfunction in human SLE. Nat. Immunol. 20, 1071\u20131082 (2019).","journal-title":"Nat. Immunol."},{"key":"1365_CR104","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.trsl.2008.10.007","volume":"153","author":"Y Pan","year":"2009","unstructured":"Pan, Y. & Sawalha, A. H. Epigenetic regulation and the pathogenesis of systemic lupus erythematosus. Transl. Res. 153, 4\u201310 (2009).","journal-title":"Transl. Res."},{"key":"1365_CR105","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/s41590-020-0678-5","volume":"21","author":"R Vijay","year":"2020","unstructured":"Vijay, R. et al. Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria. Nat. Immunol. 21, 790\u2013801 (2020).","journal-title":"Nat. Immunol."},{"key":"1365_CR106","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41577-019-0244-2","volume":"20","author":"M Akkaya","year":"2020","unstructured":"Akkaya, M., Kwak, K. & Pierce, S. K. B cell memory: building two walls of protection against pathogens. Nat. Rev. Immunol. 20, 229\u2013238 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1365_CR107","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41590-025-02102-0","volume":"26","author":"E Martinis","year":"2025","unstructured":"Martinis, E. et al. B cell immunometabolism in health and disease. Nat. Immunol. 26, 366\u2013377 (2025).","journal-title":"Nat. Immunol."},{"key":"1365_CR108","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.immuni.2017.06.005","volume":"46","author":"J Ersching","year":"2017","unstructured":"Ersching, J. et al. Germinal center selection and affinity maturation require dynamic regulation of mTORC1 kinase. Immunity 46, 1045\u20131058.e6 (2017).","journal-title":"Immunity"},{"key":"1365_CR109","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201699","volume":"218","author":"J Pae","year":"2021","unstructured":"Pae, J. et al. Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells. J. Exp. Med. 218, e20201699 (2021).","journal-title":"J. Exp. Med."},{"key":"1365_CR110","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1038\/s41590-023-01540-y","volume":"24","author":"R Sharma","year":"2023","unstructured":"Sharma, R. et al. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nat. Immunol. 24, 1358\u20131369 (2023).","journal-title":"Nat. Immunol."},{"key":"1365_CR111","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1038\/s41590-020-00814-z","volume":"21","author":"MC Woodruff","year":"2020","unstructured":"Woodruff, M. C. et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat. Immunol. 21, 1506\u20131516 (2020).","journal-title":"Nat. Immunol."},{"key":"1365_CR112","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41586-022-05273-0","volume":"611","author":"MC Woodruff","year":"2022","unstructured":"Woodruff, M. C. et al. Dysregulated naive B cells and de novo autoreactivity in severe COVID-19. Nature 611, 139\u2013147 (2022).","journal-title":"Nature"},{"key":"1365_CR113","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1025","volume":"12","author":"T Cao","year":"2022","unstructured":"Cao, T. et al. Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity. Clin. Transl. Med. 12, e1025 (2022).","journal-title":"Clin. Transl. Med."},{"key":"1365_CR114","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41584-025-01267-0","volume":"21","author":"E Pati\u00f1o-Martinez","year":"2025","unstructured":"Pati\u00f1o-Martinez, E. & Kaplan, M. J. Immunometabolism in systemic lupus erythematosus. Nat. Rev. Rheumatol. 21, 377\u2013395 (2025).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1365_CR115","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adu6015","volume":"17","author":"Q Zeng","year":"2025","unstructured":"Zeng, Q. et al. The m6A demethylase FTO links TLR7 to mitochondrial oxidation driving age-associated B cell formation in systemic lupus erythematosus. Sci. Transl. Med. 17, eadu6015 (2025).","journal-title":"Sci. Transl. Med."},{"key":"1365_CR116","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-37083-x","volume":"14","author":"E Gomez-Ba\u00f1uelos","year":"2023","unstructured":"Gomez-Ba\u00f1uelos, E. et al. Affinity maturation generates pathogenic antibodies with dual reactivity to DNase1L3 and dsDNA in systemic lupus erythematosus. Nat. Commun. 14, 1\u201314 (2023).","journal-title":"Nat. Commun."},{"key":"1365_CR117","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1084\/jem.171.1.265","volume":"171","author":"M Shlomchik","year":"1990","unstructured":"Shlomchik, M. et al. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J. Exp. Med. 171, 265\u2013297 (1990).","journal-title":"J. Exp. Med."},{"key":"1365_CR118","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adi8150","volume":"9","author":"T van den Broek","year":"2024","unstructured":"van den Broek, T. et al. Invasion of spontaneous germinal centers by naive B cells is rapid and persistent. Sci. Immunol. 9, eadi8150 (2024).","journal-title":"Sci. Immunol."},{"key":"1365_CR119","doi-asserted-by":"publisher","first-page":"E2567","DOI":"10.1073\/pnas.1406974111","volume":"111","author":"Z Sabouri","year":"2014","unstructured":"Sabouri, Z. et al. Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity. Proc. Natl Acad. Sci. USA 111, E2567\u2013E2575 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR120","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/imr.12808","volume":"292","author":"DL Burnett","year":"2019","unstructured":"Burnett, D. L., Reed, J. H., Christ, D. & Goodnow, C. C. Clonal redemption and clonal anergy as mechanisms to balance B cell tolerance and immunity. Immunol. Rev. 292, 61\u201375 (2019).","journal-title":"Immunol. Rev."},{"key":"1365_CR121","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/sji.13192","volume":"95","author":"EH Akama-Garren","year":"2022","unstructured":"Akama-Garren, E. H. & Carroll, M. C. T cell help in the autoreactive germinal center. Scand. J. Immunol. 95, 1\u201325 (2022).","journal-title":"Scand. J. Immunol."},{"key":"1365_CR122","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.immuni.2013.09.007","volume":"39","author":"J He","year":"2013","unstructured":"He, J. et al. Circulating precursor CCR7loPD-1hi CXCR5+ CD4+ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity 39, 770\u2013781 (2013).","journal-title":"Immunity"},{"key":"1365_CR123","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.4049\/jimmunol.2200098","volume":"208","author":"EH Akama-Garren","year":"2022","unstructured":"Akama-Garren, E. H. & Carroll, M. C. Lupus susceptibility loci predispose mice to clonal lymphocytic responses and myeloid expansion. J. Immunol. 208, 2403\u20132424 (2022).","journal-title":"J. Immunol."},{"key":"1365_CR124","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/art.25032","volume":"62","author":"N Simpson","year":"2010","unstructured":"Simpson, N. et al. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum. 62, 234\u2013244 (2010).","journal-title":"Arthritis Rheum."},{"key":"1365_CR125","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/827480","volume":"2012","author":"J Ma","year":"2012","unstructured":"Ma, J. et al. Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis. Clin. Dev. Immunol. 2012, 827480 (2012).","journal-title":"Clin. Dev. Immunol."},{"key":"1365_CR126","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.clim.2013.02.024","volume":"147","author":"K Szabo","year":"2013","unstructured":"Szabo, K. et al. Follicular helper T cells may play an important role in the severity of primary Sj\u00f6gren\u2019s syndrome. Clin. Immunol. 147, 95\u2013104 (2013).","journal-title":"Clin. Immunol."},{"key":"1365_CR127","doi-asserted-by":"publisher","DOI":"10.1186\/ar1928","volume":"8","author":"M Kawamoto","year":"2006","unstructured":"Kawamoto, M. et al. Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-\u03b3 and anti-double-stranded DNA antibody production. Arthritis Res. Ther. 8, R62 (2006).","journal-title":"Arthritis Res. Ther."},{"key":"1365_CR128","doi-asserted-by":"publisher","first-page":"832","DOI":"10.4049\/jimmunol.1500759","volume":"195","author":"T Dhaeze","year":"2015","unstructured":"Dhaeze, T. et al. Circulating follicular regulatory T cells are defective in multiple sclerosis. J. Immunol. 195, 832\u2013840 (2015).","journal-title":"J. Immunol."},{"key":"1365_CR129","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan1487","volume":"2","author":"VR Fonseca","year":"2017","unstructured":"Fonseca, V. R. et al. Human blood Tfr cells are indicators of ongoing humoral activity not fully licensed with suppressive function. Sci. Immunol. 2, eaan1487 (2017).","journal-title":"Sci. Immunol."},{"key":"1365_CR130","doi-asserted-by":"publisher","first-page":"19432","DOI":"10.1073\/pnas.1010603107","volume":"107","author":"K Kawane","year":"2010","unstructured":"Kawane, K., Tanaka, H., Kitahara, Y., Shimaoka, S. & Nagata, S. Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation. Proc. Natl Acad. Sci. USA 107, 19432\u201319437 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR131","doi-asserted-by":"publisher","first-page":"9604","DOI":"10.1073\/pnas.1808594115","volume":"115","author":"P-G Ritvo","year":"2018","unstructured":"Ritvo, P.-G. et al. High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells. Proc. Natl Acad. Sci. USA 115, 9604\u20139609 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR132","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-27035-8","volume":"12","author":"EH Akama-Garren","year":"2021","unstructured":"Akama-Garren, E. H. et al. Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease. Nat. Commun. 12, 1\u201319 (2021).","journal-title":"Nat. Commun."},{"key":"1365_CR133","doi-asserted-by":"publisher","first-page":"4305","DOI":"10.4049\/jimmunol.165.8.4305","volume":"165","author":"G Eberl","year":"2000","unstructured":"Eberl, G., Brawand, P. & MacDonald, H. R. Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation. J. Immunol. 165, 4305\u20134311 (2000).","journal-title":"J. Immunol."},{"key":"1365_CR134","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1126\/science.272.5270.1947","volume":"272","author":"DF Tough","year":"1996","unstructured":"Tough, D. F., Borrow, P. & Sprent, J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947\u20131950 (1996).","journal-title":"Science"},{"key":"1365_CR135","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.immuni.2009.01.009","volume":"30","author":"M Harkiolaki","year":"2009","unstructured":"Harkiolaki, M. et al. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity 30, 348\u2013357 (2009).","journal-title":"Immunity"},{"key":"1365_CR136","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/S0167-5699(98)01299-7","volume":"19","author":"D Mason","year":"1998","unstructured":"Mason, D. A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19, 395\u2013404 (1998).","journal-title":"Immunol. Today"},{"key":"1365_CR137","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.cell.2022.11.032","volume":"186","author":"T H\u00e4ggl\u00f6f","year":"2023","unstructured":"H\u00e4ggl\u00f6f, T. et al. Continuous germinal center invasion contributes to the diversity of the immune response. Cell 186, 147\u2013161.e15 (2023).","journal-title":"Cell"},{"key":"1365_CR138","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/0167-5699(96)80565-2","volume":"17","author":"D Nemazee","year":"1996","unstructured":"Nemazee, D. Antigen receptor \u2018capacity\u2019 and the sensitivity of self-tolerance. Immunol. Today 17, 25\u201329 (1996).","journal-title":"Immunol. Today"},{"key":"1365_CR139","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1126\/science.286.5447.2156","volume":"286","author":"AF Ochsenbein","year":"1999","unstructured":"Ochsenbein, A. F. et al. Control of early viral and bacterial distribution and disease by natural antibodies. Science 286, 2156\u20132159 (1999).","journal-title":"Science"},{"key":"1365_CR140","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1016\/j.cell.2022.02.012","volume":"185","author":"RD Mazor","year":"2022","unstructured":"Mazor, R. D. et al. Tumor-reactive antibodies evolve from non-binding and autoreactive precursors. Cell 185, 1208\u20131222.e21 (2022).","journal-title":"Cell"},{"key":"1365_CR141","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/imr.70005","volume":"330","author":"DY-D Zhu","year":"2025","unstructured":"Zhu, D. Y.-D., Castrillon, C. & Carroll, M. C. Innate immune receptors as dynamic modulators of extrafollicular autoimmune B cell Response. Immunol. Rev. 330, 1\u201315 (2025).","journal-title":"Immunol. Rev."},{"key":"1365_CR142","doi-asserted-by":"publisher","DOI":"10.1111\/imr.70060","volume":"334","author":"EM Flowers","year":"2025","unstructured":"Flowers, E. M., Siniscalco, E. R. & Eisenbarth, S. C. Extrafollicular and other non-germinal center B cell responses: an evolutionary perspective. Immunol. Rev. 334, e70060 (2025).","journal-title":"Immunol. Rev."},{"key":"1365_CR143","doi-asserted-by":"publisher","unstructured":"Sasaki, T. et al. Clonal relationships between Tph and Tfh cells in patients with SLE and in murine lupus. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.01.27.635189 (2025).","DOI":"10.1101\/2025.01.27.635189"},{"key":"1365_CR144","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.immuni.2022.01.002","volume":"55","author":"W Song","year":"2022","unstructured":"Song, W. et al. Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers. Immunity 55, 290\u2013307.e5 (2022).","journal-title":"Immunity"},{"key":"1365_CR145","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1084\/jem.20080840","volume":"205","author":"JM Odegard","year":"2008","unstructured":"Odegard, J. M. et al. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J. Exp. Med. 205, 2873\u20132886 (2008).","journal-title":"J. Exp. Med."},{"key":"1365_CR146","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature20810","volume":"542","author":"DA Rao","year":"2017","unstructured":"Rao, D. A. et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542, 110\u2013114 (2017).","journal-title":"Nature"},{"key":"1365_CR147","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.130062","volume":"4","author":"AV Bocharnikov","year":"2019","unstructured":"Bocharnikov, A. V. et al. PD-1hiCXCR5\u2212 T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI Insight 4, 1\u201319 (2019).","journal-title":"JCI Insight"},{"key":"1365_CR148","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2024.1327437","volume":"15","author":"Y Gartshteyn","year":"2024","unstructured":"Gartshteyn, Y. et al. SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis. Front. Immunol. 15, 1\u201313 (2024).","journal-title":"Front. Immunol."},{"key":"1365_CR149","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1084\/jem.20061660","volume":"204","author":"T Ito","year":"2007","unstructured":"Ito, T. et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204, 105\u2013115 (2007).","journal-title":"J. Exp. Med."},{"key":"1365_CR150","doi-asserted-by":"publisher","first-page":"8180","DOI":"10.4049\/jimmunol.179.12.8180","volume":"179","author":"VL Bryant","year":"2007","unstructured":"Bryant, V. L. et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J. Immunol. 179, 8180\u20138190 (2007).","journal-title":"J. Immunol."},{"key":"1365_CR151","doi-asserted-by":"publisher","first-page":"7867","DOI":"10.4049\/jimmunol.175.12.7867","volume":"175","author":"R Ettinger","year":"2005","unstructured":"Ettinger, R. et al. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J. Immunol. 175, 7867\u20137879 (2005).","journal-title":"J. Immunol."},{"key":"1365_CR152","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1182\/blood-2013-06-506865","volume":"122","author":"LJ Berglund","year":"2013","unstructured":"Berglund, L. J. et al. IL-21 signalling via STAT3 primes human n\u00e4ive B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood 122, 3940\u20133950 (2013).","journal-title":"Blood"},{"key":"1365_CR153","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1126\/science.1077002","volume":"298","author":"K Ozaki","year":"2002","unstructured":"Ozaki, K. et al. A critical role for IL-21 in regulating immunoglobulin production. Science 298, 1630\u20131634 (2002).","journal-title":"Science"},{"key":"1365_CR154","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112657","volume":"42","author":"GC Abhiraman","year":"2023","unstructured":"Abhiraman, G. C. et al. A structural blueprint for interleukin-21 signal modulation. Cell Rep. 42, 112657 (2023).","journal-title":"Cell Rep."},{"key":"1365_CR155","first-page":"1","volume":"9","author":"S Wang","year":"2018","unstructured":"Wang, S. et al. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE. Nat. Commun. 9, 1\u201314 (2018).","journal-title":"Nat. Commun."},{"key":"1365_CR156","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.4049\/jimmunol.2300027","volume":"210","author":"W Song","year":"2023","unstructured":"Song, W. et al. IL-21 and tissue-specific signals instruct Tbet+CD11c+ B cell development following viral infection Wenzhi. J. Immunol. 210, 1861\u20131865 (2023).","journal-title":"J. Immunol."},{"key":"1365_CR157","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1177\/0961203314563817","volume":"24","author":"T Tarr","year":"2015","unstructured":"Tarr, T. et al. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus. Lupus 24, 796\u2013803 (2015).","journal-title":"Lupus"},{"key":"1365_CR158","doi-asserted-by":"publisher","first-page":"3967","DOI":"10.1182\/blood-2005-10-4170","volume":"107","author":"G Cattoretti","year":"2006","unstructured":"Cattoretti, G. et al. Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells. Blood 107, 3967\u20133975 (2006).","journal-title":"Blood"},{"key":"1365_CR159","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.immuni.2015.06.013","volume":"43","author":"R Di Niro","year":"2015","unstructured":"Di Niro, R. et al. Salmonella infection drives promiscuous B cell activation followed by extrafollicular affinity maturation. Immunity 43, 120\u2013131 (2015).","journal-title":"Immunity"},{"key":"1365_CR160","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S1074-7613(02)00387-4","volume":"17","author":"H Toyama","year":"2002","unstructured":"Toyama, H. et al. Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 17, 329\u2013339 (2002).","journal-title":"Immunity"},{"key":"1365_CR161","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/intimm\/dxh241","volume":"17","author":"A Inamine","year":"2005","unstructured":"Inamine, A. et al. Two waves of memory B-cell generation in the primary immune response. Int. Immunol. 17, 581\u2013589 (2005).","journal-title":"Int. Immunol."},{"key":"1365_CR162","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.celrep.2018.06.074","volume":"24","author":"KJ Kenderes","year":"2018","unstructured":"Kenderes, K. J. et al. T-Bet+ IgM memory cells generate multi-lineage effector B cells. Cell Rep. 24, 824\u2013837.e3 (2018).","journal-title":"Cell Rep."},{"key":"1365_CR163","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108684","volume":"34","author":"HJ Sutton","year":"2021","unstructured":"Sutton, H. J. et al. Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans. Cell Rep. 34, 108684 (2021).","journal-title":"Cell Rep."},{"key":"1365_CR164","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115472","volume":"44","author":"CA Perugino","year":"2025","unstructured":"Perugino, C. A. et al. Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection. Cell Rep. 44, 115472 (2025).","journal-title":"Cell Rep."},{"key":"1365_CR165","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.41641","volume":"8","author":"E Zumaquero","year":"2019","unstructured":"Zumaquero, E. et al. IFN\u03b3 induces epigenetic programming of human T-bethi B cells and promotes TLR7\/8 and IL-21 induced differentiation. eLife 8, 1\u201336 (2019).","journal-title":"eLife"},{"key":"1365_CR166","doi-asserted-by":"publisher","first-page":"E3216","DOI":"10.1073\/pnas.1312348110","volume":"110","author":"K Rubtsova","year":"2013","unstructured":"Rubtsova, K., Rubtsov, A. V., Van Dyk, L. F., Kappler, J. W. & Marrack, P. T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance. Proc. Natl Acad. Sci. USA 110, E3216\u2013E3224 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR167","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1172\/JCI91250","volume":"127","author":"K Rubtsova","year":"2017","unstructured":"Rubtsova, K. et al. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J. Clin. Invest. 127, 1392\u20131404 (2017).","journal-title":"J. Clin. Invest."},{"key":"1365_CR168","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.4049\/jimmunol.1501209","volume":"195","author":"K Rubtsova","year":"2015","unstructured":"Rubtsova, K., Rubtsov, A. V., Cancro, M. P. & Marrack, P. Age-associated B cells: a T-bet-dependent effector with roles in protective and pathogenic immunity. J. Immunol. 195, 1933\u20131937 (2015).","journal-title":"J. Immunol."},{"key":"1365_CR169","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41590-024-02010-9","volume":"26","author":"CE Faliti","year":"2025","unstructured":"Faliti, C. E. et al. Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE. Nat. Immunol. 26, 131\u2013145 (2025).","journal-title":"Nat. Immunol."},{"key":"1365_CR170","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/s41584-024-01139-z","volume":"20","author":"G Schett","year":"2024","unstructured":"Schett, G. et al. Advancements and challenges in CAR T cell therapy in autoimmune diseases. Nat. Rev. Rheumatol. 20, 531\u2013544 (2024).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1365_CR171","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41573-020-00092-2","volume":"20","author":"DSW Lee","year":"2021","unstructured":"Lee, D. S. W., Rojas, O. L. & Gommerman, J. L. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat. Rev. Drug Discov. 20, 179\u2013199 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1365_CR172","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1038\/s41591-022-02017-5","volume":"28","author":"A Mackensen","year":"2022","unstructured":"Mackensen, A. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat. Med. 28, 2124\u20132132 (2022).","journal-title":"Nat. Med."},{"key":"1365_CR173","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","volume":"390","author":"F M\u00fcller","year":"2024","unstructured":"M\u00fcller, F. et al. CD19 CAR T-cell therapy in autoimmune disease \u2014 a case series with follow-up. N. Engl. J. Med. 390, 687\u2013700 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1365_CR174","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1182\/blood-2016-01-694356","volume":"128","author":"VG Bhoj","year":"2016","unstructured":"Bhoj, V. G. et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood 128, 360\u2013370 (2016).","journal-title":"Blood"},{"key":"1365_CR175","doi-asserted-by":"publisher","unstructured":"Grenov, A. et al. Autoantibody origins in lupus and in relapse post CAR-T therapy. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.10.20.683393 (2025).","DOI":"10.1101\/2025.10.20.683393"},{"key":"1365_CR176","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1002\/art.42750","volume":"76","author":"C Dong","year":"2024","unstructured":"Dong, C. et al. Single-cell profiling of bone marrow B cells and early B cell developmental disorders associated with systemic lupus erythematosus. Arthritis Rheumatol. 76, 599\u2013613 (2024).","journal-title":"Arthritis Rheumatol."},{"key":"1365_CR177","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.4049\/jimmunol.2101056","volume":"208","author":"SM Wemlinger","year":"2022","unstructured":"Wemlinger, S. M. et al. Preclinical analysis of candidate anti-human CD79 therapeutic antibodies using a humanized CD79 mouse model. J. Immunol. 208, 1566\u20131584 (2022).","journal-title":"J. Immunol."},{"key":"1365_CR178","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.166137","volume":"8","author":"JS Boyles","year":"2023","unstructured":"Boyles, J. S. et al. A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases. JCI Insight 8, 1\u201320 (2023).","journal-title":"JCI Insight"},{"key":"1365_CR179","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adr9382","volume":"18","author":"IJ Cohen","year":"2026","unstructured":"Cohen, I. J. et al. Chimeric antigen receptor T cells against the IGHV4-34 B cell receptor specifically eliminate neoplastic and autoimmune B cells. Sci. Transl. Med. 18, eadr9382 (2026).","journal-title":"Sci. Transl. Med."},{"key":"1365_CR180","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41586-022-04642-z","volume":"605","author":"GJ Brown","year":"2022","unstructured":"Brown, G. J. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349\u2013356 (2022).","journal-title":"Nature"},{"key":"1365_CR181","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/1074-7613(95)90179-5","volume":"3","author":"BA Jacobson","year":"1995","unstructured":"Jacobson, B. A. et al. Anatomy of autoantibody production: dominant localization of antibody-producing cells to T cell zones in Fas-deficient mice. Immunity 3, 509\u2013519 (1995).","journal-title":"Immunity"},{"key":"1365_CR182","doi-asserted-by":"publisher","first-page":"227","DOI":"10.4049\/jimmunol.133.1.227","volume":"133","author":"S Izui","year":"1984","unstructured":"Izui, S. et al. Induction of various autoantibodies by mutant gene lpr in several strains of mice. J. Immunol. 133, 227\u2013233 (1984).","journal-title":"J. Immunol."},{"key":"1365_CR183","doi-asserted-by":"publisher","first-page":"S64","DOI":"10.1002\/art.1780210909","volume":"21","author":"FJ Dixon","year":"1978","unstructured":"Dixon, F. J. et al. Etiology and pathogenesis of a spontaneous lupus-like syndrome in mice. Arthritis Rheum. 21, S64\u2013S67 (1978).","journal-title":"Arthritis Rheum."},{"key":"1365_CR184","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1126\/science.1073924","volume":"297","author":"J William","year":"2002","unstructured":"William, J., Euler, C., Christensen, S. & Shlomchik, M. J. Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297, 2066\u20132070 (2002).","journal-title":"Science"},{"key":"1365_CR185","doi-asserted-by":"publisher","first-page":"6879","DOI":"10.4049\/jimmunol.174.11.6879","volume":"174","author":"J William","year":"2005","unstructured":"William, J., Euler, C. & Shlomchik, M. J. Short-lived plasmablasts dominate the early spontaneous rheumatoid factor response: differentiation pathways, hypermutating cell types, and affinity maturation outside the germinal center. J. Immunol. 174, 6879\u20136887 (2005).","journal-title":"J. Immunol."},{"key":"1365_CR186","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.immuni.2012.08.002","volume":"37","author":"MC Carroll","year":"2012","unstructured":"Carroll, M. C. & Isenman, D. E. Regulation of humoral immunity by complement. Immunity 37, 199\u2013207 (2012).","journal-title":"Immunity"},{"key":"1365_CR187","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.18.1.393","volume":"18","author":"DT Fearon","year":"2000","unstructured":"Fearon, D. T. & Carroll, M. C. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19\/CD21 complex. Annu. Rev. Immunol. 18, 393\u2013422 (2000).","journal-title":"Annu. Rev. Immunol."},{"key":"1365_CR188","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1016\/j.molimm.2009.04.036","volume":"46","author":"MM Hoefer","year":"2009","unstructured":"Hoefer, M. M. & Illges, H. Ectodomain shedding and generation of two carboxy-terminal fragments of human complement receptor 2\/CD21. Mol. Immunol. 46, 2630\u20132639 (2009).","journal-title":"Mol. Immunol."},{"key":"1365_CR189","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1002\/eji.200323843","volume":"33","author":"M Masilamani","year":"2003","unstructured":"Masilamani, M., Kassahn, D., Mikkat, S., Glocker, M. O. & Illges, H. B cell activation leads to shedding of complement receptor type II (CR2\/CD21). Eur. J. Immunol. 33, 2391\u20132397 (2003).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR190","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/j.0300-9475.2004.01494.x","volume":"60","author":"M Masilamani","year":"2004","unstructured":"Masilamani, M. et al. Reduction of soluble complement receptor 2\/CD21 in systemic lupus erythematosus and Sj\u00f6gren's syndrome but not juvenile arthritis. Scand. J. Immunol. 60, 625\u2013630 (2004).","journal-title":"Scand. J. Immunol."},{"key":"1365_CR191","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.4049\/jimmunol.125.3.1066","volume":"125","author":"JJ Mond","year":"1980","unstructured":"Mond, J. J., Mongini, P. K., Sieckmann, D. & Paul, W. E. Role of T lymphocytes in the response to TNP-AECM-Ficoll. J. Immunol. 125, 1066\u20131070 (1980).","journal-title":"J. Immunol."},{"key":"1365_CR192","doi-asserted-by":"publisher","first-page":"5113","DOI":"10.1073\/pnas.78.8.5113","volume":"78","author":"NL Letvin","year":"1981","unstructured":"Letvin, N. L., Benacerraf, B. & Germain, R. N. B-lymphocyte responses to trinitrophenyl-conjugated Ficoll: requirement for T lymphocytes and Ia-bearing adherent cells. Proc. Natl Acad. Sci. USA 78, 5113\u20135117 (1981).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1365_CR193","doi-asserted-by":"publisher","first-page":"557","DOI":"10.4049\/jimmunol.129.2.557","volume":"129","author":"AA Nordin","year":"1982","unstructured":"Nordin, A. A. & Schreier, M. H. T cell control of the antibody response to the T-independent antigen, DAGG-Ficoll. J. Immunol. 129, 557\u2013562 (1982).","journal-title":"J. Immunol."},{"key":"1365_CR194","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1084\/jem.20102065","volume":"208","author":"SK Lee","year":"2011","unstructured":"Lee, S. K. et al. B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells. J. Exp. Med. 208, 1377\u20131388 (2011).","journal-title":"J. Exp. Med."},{"key":"1365_CR195","doi-asserted-by":"publisher","first-page":"5361","DOI":"10.4049\/jimmunol.173.9.5361","volume":"173","author":"K Ozaki","year":"2004","unstructured":"Ozaki, K. et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J. Immunol. 173, 5361\u20135371 (2004).","journal-title":"J. Immunol."},{"key":"1365_CR196","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/sciimmunol.abh0891","volume":"6","author":"B Keller","year":"2021","unstructured":"Keller, B. et al. The expansion of human T-bet high CD21 low B cells is T cell dependent. Sci. Immunol. 6, 1\u201316 (2021).","journal-title":"Sci. Immunol."},{"key":"1365_CR197","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-immunol-120419-022408","volume":"40","author":"GD Victora","year":"2022","unstructured":"Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu. Rev. Immunol. 40, 413\u2013442 (2022).","journal-title":"Annu. Rev. Immunol."},{"key":"1365_CR198","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1146\/annurev-immunol-092419-031130","volume":"38","author":"MP Cancro","year":"2020","unstructured":"Cancro, M. P. Age-associated B cells. Annu. Rev. Immunol. 38, 315\u2013340 (2020).","journal-title":"Annu. Rev. Immunol."},{"key":"1365_CR199","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.cellimm.2017.07.003","volume":"321","author":"S Portugal","year":"2017","unstructured":"Portugal, S., Obeng-Adjei, N., Moir, S., Crompton, P. D. & Pierce, S. K. Atypical memory B cells in human chronic infectious diseases: an interim report. Cell. Immunol. 321, 18\u201325 (2017).","journal-title":"Cell. Immunol."},{"key":"1365_CR200","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12824-z","volume":"10","author":"JB Wong","year":"2019","unstructured":"Wong, J. B. et al. B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage. Nat. Commun. 10, 4768 (2019).","journal-title":"Nat. Commun."},{"key":"1365_CR201","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nri1395","volume":"4","author":"J Chaudhuri","year":"2004","unstructured":"Chaudhuri, J. & Alt, F. W. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol. 4, 541\u2013552 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"1365_CR202","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1111\/imr.12813","volume":"292","author":"JL Platt","year":"2019","unstructured":"Platt, J. L., Garcia de Mattos Barbosa, M. & Cascalho, M. The five dimensions of B cell tolerance. Immunol. Rev. 292, 180\u2013193 (2019).","journal-title":"Immunol. Rev."},{"key":"1365_CR203","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1084\/jem.20151978","volume":"213","author":"JH Reed","year":"2016","unstructured":"Reed, J. H., Jackson, J., Christ, D. & Goodnow, C. C. Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization. J. Exp. Med. 213, 1255\u20131265 (2016).","journal-title":"J. Exp. Med."},{"key":"1365_CR204","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/nri2656","volume":"9","author":"S Pillai","year":"2009","unstructured":"Pillai, S. & Cariappa, A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat. Rev. Immunol. 9, 767\u2013777 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"1365_CR205","first-page":"1","volume":"23","author":"A Cerutti","year":"2011","unstructured":"Cerutti, A., Cols, M. & Puga, I. Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Bone 23, 1\u20137 (2011).","journal-title":"Bone"},{"key":"1365_CR206","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1146\/annurev.immunol.021908.132607","volume":"27","author":"JC Weill","year":"2009","unstructured":"Weill, J. C., Weller, S. & Reynaud, C. A. Human marginal zone B cells. Annu. Rev. Immunol. 27, 267\u2013285 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"1365_CR207","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.4049\/jimmunol.0804324","volume":"183","author":"NH Ruddle","year":"2009","unstructured":"Ruddle, N. H. & Akirav, E. M. Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J. Immunol. 183, 2205\u20132212 (2009).","journal-title":"J. Immunol."},{"key":"1365_CR208","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/eji.202250009","volume":"53","author":"J Leube","year":"2023","unstructured":"Leube, J. et al. Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection. Eur. J. Immunol. 53, 1\u201312 (2023).","journal-title":"Eur. J. Immunol."},{"key":"1365_CR209","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","volume":"41","author":"S Crotty","year":"2014","unstructured":"Crotty, S. T follicular helper cell differentiation, function, and roles in disease. Immunity 41, 529\u2013542 (2014).","journal-title":"Immunity"},{"key":"1365_CR210","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2021.679909","volume":"12","author":"Y Lu","year":"2021","unstructured":"Lu, Y. & Craft, J. T follicular regulatory cells: choreographers of productive germinal center responses. Front. Immunol. 12, 1\u20136 (2021).","journal-title":"Front. Immunol."}],"container-title":["Nature Reviews Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41584-026-01365-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41584-026-01365-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41584-026-01365-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:03:26Z","timestamp":1777334606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41584-026-01365-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":210,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["1365"],"URL":"https:\/\/doi.org\/10.1038\/s41584-026-01365-7","relation":{},"ISSN":["1759-4790","1759-4804"],"issn-type":[{"value":"1759-4790","type":"print"},{"value":"1759-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"27 February 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}