{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:56:28Z","timestamp":1783947388848,"version":"3.55.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL087738"],"award-info":[{"award-number":["T32 HL087738"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["T32 AR059039"],"award-info":[{"award-number":["T32 AR059039"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["T32 AR059039"],"award-info":[{"award-number":["T32 AR059039"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K12 HD043483"],"award-info":[{"award-number":["K12 HD043483"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Porter Family Fund for Autoimmunity Research"},{"name":"Vanderbilt Human Immunology Discovery Initiative"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Anti-Jo-1 autoantibodies which recognize histidyl-tRNA synthetase identify patients with the rare rheumatologic disease, anti-histidyl-tRNA synthetase syndrome (Jo-1 ARS), a phenotypically distinct subset of idiopathic inflammatory myopathies (IIM). Jo-1-binding B cells (JBCs) are implicated in disease pathogenesis, yet they have not been studied directly. We therefore aimed to characterize JBCs to better understand how they expand and function in Jo-1 ARS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We enrolled 10 IIM patients diagnosed with Jo-1 ARS, 4 patients with non-Jo-1 IIM, and 8 age- and sex-matched healthy controls. We phenotypically characterized peripheral blood mononuclear cells (PBMCs) ex vivo using flow cytometry to define the B cell subsets in which JBCs reside. We further tested their ability to differentiate into antibody-secreting cells following stimulation in vitro.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The majority of JBCs were IgM<jats:sup>+<\/jats:sup> (not class-switched). Compared to non-JBCs in the same donors, JBCs contained a higher percentage of autoimmune-prone CD21<jats:sup>lo<\/jats:sup> cells and were increased in the CD21<jats:sup>lo<\/jats:sup> IgM<jats:sup>+<\/jats:sup> IgD<jats:sup>\u2212<\/jats:sup> CD27<jats:sup>+<\/jats:sup> memory subset relative to healthy donor B cells. Whereas non-JBCs were present in the anergic B<jats:sub>ND<\/jats:sub> B cell subset, JBCs were nearly absent from this compartment. JBCs were detected among plasmablasts in some donors, but a reduced frequency of JBCs differentiated into CD38<jats:sup>hi<\/jats:sup>24<jats:sup>\u2212<\/jats:sup> plasmablasts compared to non-JBCs present in the same wells following in vitro stimulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>JBCs are enriched for autoimmune-prone CD21<jats:sup>lo<\/jats:sup> B cells, some of which exhibit a memory phenotype in the peripheral repertoire of Jo-1 ARS patients. JBCs undergo limited class switch and show reduced capacity to differentiate into antibody-secreting cells. This suggests complex B cell biology exists beyond class-switched cells that differentiate to secrete anti-Jo-1 autoantibody (i.e., what is captured through serum autoantibody studies). New Jo-1 ARS therapies should thus ideally target non-class-switched JBCs in addition to those that have undergone IgG class-switching to most effectively block cross-talk with autoreactive T cells.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-020-02412-8","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T09:02:51Z","timestamp":1611046971000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients"],"prefix":"10.1186","volume":"23","author":[{"given":"Jennifer","family":"Young-Glazer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Alberto","family":"Cisneros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Wilfong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J.","family":"Crofford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-6943","authenticated-orcid":false,"given":"Rachel H.","family":"Bonami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,19]]},"reference":[{"key":"2412_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/rheumatology\/keu289","volume":"54","author":"A Meyer","year":"2015","unstructured":"Meyer A, Meyer N, Schaeffer M, Gottenberg J-E, Geny B, Sibilia J. Incidence and prevalence of inflammatory myopathies: a systematic review. Rheumatology (Oxford). 2015;54:50\u201363.","journal-title":"Rheumatology (Oxford)"},{"key":"2412_CR2","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1056\/NEJM197502132920706","volume":"292","author":"A Bohan","year":"1975","unstructured":"Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344\u20137.","journal-title":"N Engl J Med"},{"key":"2412_CR3","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJM197502202920807","volume":"292","author":"A Bohan","year":"1975","unstructured":"Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403\u20137.","journal-title":"N Engl J Med"},{"key":"2412_CR4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrrheum.2018.56","volume":"14","author":"NJ McHugh","year":"2018","unstructured":"McHugh NJ, Tansley SL. Autoantibodies in myositis. Nat Rev Rheumatol. 2018;14:290\u2013302.","journal-title":"Nat Rev Rheumatol"},{"key":"2412_CR5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.autrev.2014.01.022","volume":"13","author":"M Mahler","year":"2014","unstructured":"Mahler M, Miller FW, Fritzler MJ. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev. 2014;13:367\u201371.","journal-title":"Autoimmun Rev"},{"key":"2412_CR6","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s13075-018-1650-8","volume":"20","author":"O Kry\u0161t\u016ffkov\u00e1","year":"2018","unstructured":"Kry\u0161t\u016ffkov\u00e1 O, Hulejov\u00e1 H, Mann HF, Pecha O, P\u016ftov\u00e1 I, Ekholm L, et al. Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis. Arthritis Res Ther. 2018;20:158.","journal-title":"Arthritis Res Ther"},{"key":"2412_CR7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/1529-0131(199902)42:2<291::AID-ANR11>3.0.CO;2-1","volume":"42","author":"T Sugiura","year":"1999","unstructured":"Sugiura T, Murakawa Y, Nagai A, Kondo M, Kobayashi S. Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T cells cause muscle cell injury directly in polymyositis. Arthritis Rheum. 1999;42:291\u20138.","journal-title":"Arthritis Rheum"},{"key":"2412_CR8","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1136\/ard.2008.091405","volume":"68","author":"O Krystufkov\u00e1","year":"2009","unstructured":"Krystufkov\u00e1 O, Vallerskog T, Helmers SB, Mann H, Putov\u00e1 I, Bel\u00e1cek J, et al. Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis. 2009;68:836\u201343.","journal-title":"Ann Rheum Dis"},{"key":"2412_CR9","first-page":"991","volume":"55","author":"R Aggarwal","year":"2016","unstructured":"Aggarwal R, Oddis CV, Goudeau D, Koontz D, Qi Z, Reed AM, et al. Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. Rheumatol (United Kingdom). 2016;55:991\u20139.","journal-title":"Rheumatol (United Kingdom)"},{"key":"2412_CR10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/rheumatology\/kew146","volume":"56","author":"S Fasano","year":"2017","unstructured":"Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology. 2017;56:26\u201336.","journal-title":"Rheumatology."},{"key":"2412_CR11","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1002\/eji.201343315","volume":"44","author":"D McIntyre","year":"2014","unstructured":"McIntyre D, Zuckerman NS, Field M, Mehr R, Stott DI. The V(H) repertoire and clonal diversification of B cells in inflammatory myopathies. Eur J Immunol. 2014;44:585\u201396.","journal-title":"Eur J Immunol"},{"key":"2412_CR12","doi-asserted-by":"publisher","first-page":"547","DOI":"10.4049\/jimmunol.178.1.547","volume":"178","author":"EM Bradshaw","year":"2007","unstructured":"Bradshaw EM, Orihuela A, McArdel SL, Salajegheh M, Amato AA, Hafler DA, et al. A local antigen-driven humoral response is present in the inflammatory myopathies. J Immunol. 2007;178:547\u201356.","journal-title":"J Immunol"},{"key":"2412_CR13","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1172\/JCI114461","volume":"85","author":"FW Miller","year":"1990","unstructured":"Miller FW, Twitty SA, Biswas T, Plotz PH. Origin and regulation of a disease-specific autoantibody response. Antigenic epitopes, spectrotype stability, and isotype restriction of anti-Jo-1 autoantibodies. J Clin Invest. 1990;85:468\u201375.","journal-title":"J Clin Invest"},{"key":"2412_CR14","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1096\/fasebj.9.12.7672516","volume":"9","author":"A Martin","year":"1995","unstructured":"Martin A, Shulman MJ, Tsui FW. Epitope studies indicate that histidyl-tRNA synthetase is a stimulating antigen in idiopathic myositis. FASEB J. 1995;9:1226\u201333.","journal-title":"FASEB J"},{"key":"2412_CR15","doi-asserted-by":"publisher","first-page":"24277","DOI":"10.1016\/S0021-9258(19)51078-X","volume":"269","author":"N Raben","year":"1994","unstructured":"Raben N, Nichols R, Dohlman J, McPhie P, Sridhar V, Hyde C, et al. A motif in human histidyl-tRNA synthetase which is shared among several aminoacyl-tRNA synthetases is a coiled-coil that is essential for enzymatic activity and contains the major autoantigenic epitope. J Biol Chem. 1994;269:24277\u201383.","journal-title":"J Biol Chem"},{"key":"2412_CR16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/01.md.0000217525.82287.eb","volume":"85","author":"TP O\u2019Hanlon","year":"2006","unstructured":"O\u2019Hanlon TP, Carrick DM, Targoff IN, Arnett FC, Reveille JD, Carrington M, et al. Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies. Medicine (Baltimore). 2006;85:111\u201327.","journal-title":"Medicine (Baltimore)"},{"key":"2412_CR17","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1136\/annrheumdis-2019-215046","volume":"78","author":"S Rothwell","year":"2019","unstructured":"Rothwell S, Chinoy H, Lamb JA, Miller FW, Rider LG, Wedderburn LR, et al. Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups. Ann Rheum Dis. 2019;78:996\u20131002.","journal-title":"Ann Rheum Dis"},{"key":"2412_CR18","doi-asserted-by":"publisher","first-page":"9933","DOI":"10.1073\/pnas.87.24.9933","volume":"87","author":"FW Miller","year":"1990","unstructured":"Miller FW, Waite KA, Biswas T, Plotz PH. The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity. Proc Natl Acad Sci U S A. 1990;87:9933\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2412_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.123387","volume":"3","author":"MA Wurth","year":"2018","unstructured":"Wurth MA, Hadadianpour A, Horvath DJ, Daniel J, Bogdan O, Goleniewska K, et al. Human IgE mAbs define variability in commercial Aspergillus extract allergen composition. JCI insight. 2018;3:1\u201310.","journal-title":"JCI insight"},{"key":"2412_CR20","doi-asserted-by":"publisher","first-page":"5026","DOI":"10.1182\/blood-2009-09-243071","volume":"115","author":"I Isnardi","year":"2010","unstructured":"Isnardi I, Ng Y, Menard L, Meyers G, Saadoun D, Srdanovic I, et al. Complement receptor 2\/CD21- human naive B cells contain mostly autoreactive unresponsive clones. Blood. 2010;115:5026\u201336.","journal-title":"Blood."},{"key":"2412_CR21","doi-asserted-by":"publisher","first-page":"827","DOI":"10.4049\/jimmunol.174.2.827","volume":"174","author":"CA Acevedo-Su\u00e1rez","year":"2005","unstructured":"Acevedo-Su\u00e1rez CA, Hulbert C, Woodward EJ, Thomas JW. Uncoupling of anergy from developmental arrest in anti-insulin B cells supports the development of autoimmune diabetes. J Immunol. 2005;174:827\u201333.","journal-title":"J Immunol"},{"key":"2412_CR22","doi-asserted-by":"publisher","first-page":"861","DOI":"10.4049\/jimmunol.1701717","volume":"201","author":"JL Felton","year":"2018","unstructured":"Felton JL, Maseda D, Bonami RH, Hulbert C, Thomas JW. Anti-insulin B cells are poised for antigen presentation in type 1 diabetes. J Immunol. 2018;201:861\u201373.","journal-title":"J Immunol"},{"key":"2412_CR23","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/334676a0","volume":"334","author":"CC Goodnow","year":"1988","unstructured":"Goodnow CC, Crosbie J, Adelstein S, Lavoie TB, Smith-Gill SJ, Brink RA, et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988;334:676\u201382.","journal-title":"Nature."},{"key":"2412_CR24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1084\/jem.20080611","volume":"206","author":"JA Duty","year":"2009","unstructured":"Duty JA, Szodoray P, Zheng N-Y, Koelsch KA, Zhang Q, Swiatkowski M, et al. Functional anergy in a subpopulation of naive B cells from healthy humans that express autoreactive immunoglobulin receptors. J Exp Med. 2009;206:139\u201351.","journal-title":"J Exp Med"},{"key":"2412_CR25","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.4049\/jimmunol.1001946","volume":"186","author":"TD Qu\u00e1ch","year":"2011","unstructured":"Qu\u00e1ch TD, Manjarrez-Ordu\u00f1o N, Adlowitz DG, Silver L, Yang H, Wei C, et al. Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM. J Immunol. 2011;186:4640\u20138.","journal-title":"J Immunol"},{"key":"2412_CR26","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/art.37828","volume":"65","author":"D Saadoun","year":"2013","unstructured":"Saadoun D, Terrier B, Bannock J, Vazquez T, Massad C, Kang I, et al. Expansion of autoreactive unresponsive CD21-\/low B cells in Sj\u00f6gren\u2019s syndrome-associated lymphoproliferation. Arthritis Rheum. 2013;65:1085\u201396.","journal-title":"Arthritis Rheum"},{"key":"2412_CR27","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1126\/sciimmunol.aai8153","volume":"2","author":"D Lau","year":"2017","unstructured":"Lau D, Lan LY-L, Andrews SF, Henry C, Rojas KT, Neu KE, et al. Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation. Sci Immunol. 2017;2:139\u201348.","journal-title":"Sci Immunol"},{"key":"2412_CR28","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.4049\/jimmunol.2000343","volume":"205","author":"M Freudenhammer","year":"2020","unstructured":"Freudenhammer M, Voll RE, Binder SC, Keller B, Warnatz K. Naive- and memory-like CD21low B cell subsets share core phenotypic and signaling characteristics in systemic autoimmune disorders. J Immunol. 2020;205:2016\u201325.","journal-title":"J Immunol"},{"key":"2412_CR29","doi-asserted-by":"publisher","first-page":"535784","DOI":"10.3389\/fimmu.2020.535784","volume":"11","author":"ME Reincke","year":"2020","unstructured":"Reincke ME, Payne KJ, Harder I, Strohmeier V, Voll RE, Warnatz K, et al. The antigen presenting potential of CD21low B cells. Front Immunol. 2020;11:535784.","journal-title":"Front Immunol"},{"key":"2412_CR30","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/art.40352","volume":"70","author":"S Glauzy","year":"2018","unstructured":"Glauzy S, Boccitto M, Bannock JM, Delmotte FR, Saadoun D, Cacoub P, et al. Accumulation of antigen-driven lymphoproliferations in complement receptor 2\/CD21\u2212\/low B cells from patients with Sj\u00f6gren\u2019s syndrome. Arthritis Rheumatol. 2018;70:298\u2013307.","journal-title":"Arthritis Rheumatol"},{"key":"2412_CR31","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.3389\/fimmu.2019.02458","volume":"10","author":"I Sanz","year":"2019","unstructured":"Sanz I, Wei C, Jenks SA, Cashman KS, Tipton C, Woodruff MC, et al. Challenges and opportunities for consistent classification of human B cell and plasma cell populations. Front Immunol. 2019;10:2458.","journal-title":"Front Immunol"},{"key":"2412_CR32","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1126\/science.1086907","volume":"301","author":"H Wardemann","year":"2003","unstructured":"Wardemann H. Predominant autoantibody production by early human B cell precursors. Science (80- ). 2003;301:1374\u20137.","journal-title":"Science (80- )"},{"key":"2412_CR33","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1002\/art.40215","volume":"69","author":"S Glauzy","year":"2017","unstructured":"Glauzy S, Sng J, Bannock JM, Gottenberg J-E, Korganow A-S, Cacoub P, et al. Defective early B cell tolerance checkpoints in Sj\u00f6gren\u2019s syndrome patients. Arthritis Rheumatol (Hoboken, NJ). 2017;69:2203\u20138.","journal-title":"Arthritis Rheumatol (Hoboken, NJ)"},{"key":"2412_CR34","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. 2011;1246:1\u201310.","journal-title":"Ann N Y Acad Sci"},{"key":"2412_CR35","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1084\/jem.20042251","volume":"201","author":"S Yurasov","year":"2005","unstructured":"Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med. 2005;201:703\u201311.","journal-title":"J Exp Med"},{"key":"2412_CR36","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1084\/jem.20042321","volume":"201","author":"J Samuels","year":"2005","unstructured":"Samuels J, Ng Y-S, Coupillaud C, Paget D, Meffre E. Impaired early B cell tolerance in patients with rheumatoid arthritis. J Exp Med. 2005;201:1659\u201367.","journal-title":"J Exp Med"},{"key":"2412_CR37","doi-asserted-by":"publisher","first-page":"5514","DOI":"10.4049\/jimmunol.1002932","volume":"186","author":"FE-H Lee","year":"2011","unstructured":"Lee FE-H, Halliley JL, Walsh EE, Moscatiello AP, Kmush BL, Falsey AR, et al. Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect. J Immunol. 2011;186:5514\u201321.","journal-title":"J Immunol"},{"key":"2412_CR38","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nature06890","volume":"453","author":"J Wrammert","year":"2008","unstructured":"Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453:667\u201371.","journal-title":"Nature."},{"key":"2412_CR39","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/imr.12821","volume":"292","author":"E Meffre","year":"2019","unstructured":"Meffre E, O\u2019Connor KC. Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev. 2019;292:90\u2013101.","journal-title":"Immunol Rev"},{"key":"2412_CR40","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.2337\/db11-1746","volume":"61","author":"RA Henry","year":"2012","unstructured":"Henry RA, Kendall PL, Thomas JW. Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes. Diabetes. 2012;61:2037\u201344.","journal-title":"Diabetes."},{"key":"2412_CR41","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1126\/science.aaf6756","volume":"353","author":"CT Ellebrecht","year":"2016","unstructured":"Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ, et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016;353:179\u201384.","journal-title":"Science."},{"key":"2412_CR42","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jneuroim.2019.04.014","volume":"332","author":"G Dzangu\u00e9-Tchoupou","year":"2019","unstructured":"Dzangu\u00e9-Tchoupou G, Allenbach Y, Preu\u00dfe C, Stenzel W, Benveniste O. Mass cytometry reveals an impairment of B cell homeostasis in anti-synthetase syndrome. J Neuroimmunol Elsevier. 2019;332:212\u20135.","journal-title":"J Neuroimmunol Elsevier"},{"key":"2412_CR43","doi-asserted-by":"crossref","unstructured":"Della Valle L, Dohmen SE, Verhagen OJHM, Berkowska MA, Vidarsson G, Ellen van der Schoot C. The majority of human memory B cells recognizing RhD and tetanus resides in IgM+ B cells. J Immunol 2014;193:1071\u20131079.","DOI":"10.4049\/jimmunol.1400706"},{"key":"2412_CR44","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.3389\/fimmu.2018.01372","volume":"9","author":"CJM Piper","year":"2018","unstructured":"Piper CJM, Wilkinson MGL, Deakin CT, Otto GW, Dowle S, Duurland CL, et al. CD19+CD24hiCD38hi B cells are expanded in juvenile dermatomyositis and exhibit a pro-inflammatory phenotype after activation through toll-like receptor 7 and interferon-\u03b1. Front Immunol. 2018;9:1372.","journal-title":"Front Immunol"},{"key":"2412_CR45","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.2337\/db13-1798","volume":"64","author":"MJ Smith","year":"2015","unstructured":"Smith MJ, Packard TA, O\u2019Neill SK, Henry Dunand CJ, Huang M, Fitzgerald-Miller L, et al. Loss of anergic B cells in prediabetic and new-onset type 1 diabetic patients. Diabetes. 2015;64:1703\u201312.","journal-title":"Diabetes."},{"key":"2412_CR46","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jaut.2017.12.001","volume":"89","author":"MJ Smith","year":"2018","unstructured":"Smith MJ, Rihanek M, Coleman BM, Gottlieb PA, Sarapura VD, Cambier JC. Activation of thyroid antigen-reactive B cells in recent onset autoimmune thyroid disease patients. J Autoimmun. 2018;89:82\u20139.","journal-title":"J Autoimmun"},{"key":"2412_CR47","doi-asserted-by":"publisher","first-page":"eaaw4626","DOI":"10.1126\/scitranslmed.aaw4626","volume":"11","author":"KA Mensah","year":"2019","unstructured":"Mensah KA, Chen JW, Schickel J-N, Isnardi I, Yamakawa N, Vega-Loza A, et al. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Sci Transl Med. 2019;11:eaaw4626.","journal-title":"Sci Transl Med."},{"key":"2412_CR48","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.immuni.2018.08.015","volume":"49","author":"SA Jenks","year":"2018","unstructured":"Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, et al. Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity. 2018;49:725\u201339 e6.","journal-title":"Immunity"},{"key":"2412_CR49","doi-asserted-by":"publisher","first-page":"7127","DOI":"10.4049\/jimmunol.169.12.7127","volume":"169","author":"DP Ascherman","year":"2002","unstructured":"Ascherman DP, Oriss TB, Oddis CV, Wright TM. Critical requirement for professional APCs in eliciting T cell responses to novel fragments of histidyl-tRNA synthetase (Jo-1) in Jo-1 antibody-positive polymyositis. J Immunol. 2002;169:7127\u201334.","journal-title":"J Immunol"},{"key":"2412_CR50","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.4049\/jimmunol.1202104","volume":"190","author":"PL Kendall","year":"2013","unstructured":"Kendall PL, Case JB, Sullivan AM, Holderness JS, Wells KS, Liu E, et al. Tolerant anti-insulin B cells are effective APCs. J Immunol. 2013;190:2519\u201326.","journal-title":"J Immunol"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02412-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-020-02412-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02412-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T09:32:27Z","timestamp":1611048747000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-02412-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,19]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2412"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-02412-8","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,19]]},"assertion":[{"value":"22 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Participants consented to these studies, which were approved by the Vanderbilt Institutional Review Board.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare there are no financial or non-financial competing interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33"}}