{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:38:22Z","timestamp":1791725902387,"version":"4.3.4"},"reference-count":66,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1,11]]},"abstract":"<jats:p>The mechanisms by which B cells undergo tolerance, such as receptor editing, clonal deletion, and anergy, have been established in mice. However, corroborating these mechanisms in humans remains challenging. To study how autoreactive human B cells undergo tolerance, we developed a novel humanized mouse model. Mice expressing an anti\u2013human Ig\u03ba membrane protein to serve as a ubiquitous neo self-antigen (Ag) were transplanted with a human immune system. By following the fate of self-reactive human \u03ba+ B cells relative to nonautoreactive \u03bb+ cells, we show that tolerance of human B cells occurs at the first site of self-Ag encounter, the bone marrow, via a combination of receptor editing and clonal deletion. Moreover, the amount of available self-Ag and the genetics of the cord blood donor dictate the levels of central tolerance and autoreactive B cells in the periphery. Thus, this model can be useful for studying specific mechanisms of human B cell tolerance and to reveal differences in the extent of this process among human populations.<\/jats:p>","DOI":"10.1084\/jem.20151039","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T20:17:56Z","timestamp":1450815476000},"page":"93-108","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Receptor editing and genetic variability in human autoreactive B cells"],"prefix":"10.1084","volume":"213","author":[{"given":"Julie","family":"Lang","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Department of Biomedical Research, National Jewish Health, Denver, CO 80206 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Department of Biomedical Research, National Jewish Health, Denver, CO 80206 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Strauch","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Department of Biomedical Research, National Jewish Health, Denver, CO 80206 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Freed","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Division of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, CO 80045 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul M.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Department of Biomedical Research, National Jewish Health, Denver, CO 80206 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nemazee","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pelanda","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO 80045 1"},{"name":"Department of Biomedical Research, National Jewish Health, Denver, CO 80206 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"2023072603182181900_bib1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1084\/jem.20041854","article-title":"An immunoglobulin C\u03ba-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system","volume":"201","author":"Ait-Azzouzene","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib2","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/j.0105-2896.2004.0106.x","article-title":"Tolerance-induced receptor selection: scope, sensitivity, locus specificity, and relationship to lymphocyte-positive selection","volume":"197","author":"A\u00eft-Azzouzene","year":"2004","journal-title":"Immunol. Rev."},{"key":"2023072603182181900_bib3","doi-asserted-by":"publisher","first-page":"939","DOI":"10.4049\/jimmunol.176.2.939","article-title":"Split tolerance in peripheral B cell subsets in mice expressing a low level of Ig\u03ba-reactive ligand","volume":"176","author":"A\u00eft-Azzouzene","year":"2006","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.coi.2013.03.009","article-title":"Human immune responses and potential for vaccine assessment in humanized mice","volume":"25","author":"Akkina","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"2023072603182181900_bib5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1084\/jem.20120525","article-title":"Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity","volume":"210","author":"Andrews","year":"2013","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib6","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1002\/1521-4141(200112)31:12&lt;3631::AID-IMMU3631&gt;3.0.CO;2-L","article-title":"Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human","volume":"31","author":"Br\u00e4uninger","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2023072603182181900_bib7","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1126\/science.1056600","article-title":"Contribution of receptor editing to the antibody repertoire","volume":"291","author":"Casellas","year":"2001","journal-title":"Science."},{"key":"2023072603182181900_bib8","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s10875-010-9478-2","article-title":"Human B cell development and antibody production in humanized NOD\/SCID\/IL-2R\u03b3null (NSG) mice conditioned by busulfan","volume":"31","author":"Choi","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"2023072603182181900_bib9","doi-asserted-by":"publisher","first-page":"3834","DOI":"10.4049\/jimmunol.181.6.3834","article-title":"B cell receptor affinity and B cell subset identity integrate to define the effectiveness, affinity threshold, and mechanism of anergy","volume":"181","author":"Diz","year":"2008","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib10","doi-asserted-by":"publisher","first-page":"11264","DOI":"10.1073\/pnas.0604053103","article-title":"Consequences of receptor editing at the \u03bb locus: Multireactivity and light chain secretion","volume":"103","author":"Doyle","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072603182181900_bib11","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.4049\/jimmunol.0903564","article-title":"Peripheral B cell tolerance and function in transgenic mice expressing an IgD superantigen","volume":"184","author":"Duong","year":"2010","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib12","doi-asserted-by":"publisher","first-page":"5596","DOI":"10.4049\/jimmunol.1102479","article-title":"Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape","volume":"187","author":"Duong","year":"2011","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib13","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1084\/jem.20120332","article-title":"Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice","volume":"209","author":"Fournier","year":"2012","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0065-2776(08)60633-1","article-title":"Self-tolerance checkpoints in B lymphocyte development","volume":"59","author":"Goodnow","year":"1995","journal-title":"Adv. Immunol."},{"key":"2023072603182181900_bib15","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/ni.1900","article-title":"Control systems and decision making for antibody production","volume":"11","author":"Goodnow","year":"2010","journal-title":"Nat. Immunol."},{"key":"2023072603182181900_bib16","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.1128\/JVI.02010-06","article-title":"Human immunodeficiency virus type 1 pathobiology studied in humanized BALB\/c-Rag2\u2212\/\u2212\u03b3c\u2212\/\u2212 mice","volume":"81","author":"Gorantla","year":"2007","journal-title":"J. Virol."},{"key":"2023072603182181900_bib17","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1002\/eji.1830240616","article-title":"Negative selection of multireactive B cell clones in normal adult mice","volume":"24","author":"Grandien","year":"1994","journal-title":"Eur. J. Immunol."},{"key":"2023072603182181900_bib18","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/ni1076","article-title":"Receptor editing is the main mechanism of B cell tolerance toward membrane antigens","volume":"5","author":"Halverson","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023072603182181900_bib19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/0092-8674(93)90111-3","article-title":"Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death","volume":"72","author":"Hartley","year":"1993","journal-title":"Cell."},{"key":"2023072603182181900_bib20","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1126\/science.285.5424.113","article-title":"Positive selection of natural autoreactive B cells","volume":"285","author":"Hayakawa","year":"1999","journal-title":"Science."},{"key":"2023072603182181900_bib21","doi-asserted-by":"publisher","first-page":"909","DOI":"10.4049\/jimmunol.175.2.909","article-title":"In vivo assessment of the relative contributions of deletion, anergy, and editing to B cell self-tolerance","volume":"175","author":"Hippen","year":"2005","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib22","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1038\/cmi.2012.2","article-title":"Current advances in humanized mouse models","volume":"9","author":"Ito","year":"2012","journal-title":"Cell. Mol. Immunol."},{"key":"2023072603182181900_bib23","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1084\/jem.20122340","article-title":"Light chain editors of anti-DNA receptors in human B cells","volume":"211","author":"Kalinina","year":"2014","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib24","doi-asserted-by":"publisher","first-page":"367","DOI":"10.4049\/jimmunol.174.1.367","article-title":"Tracing the pre-B to immature B cell transition in human leukemia cells reveals a coordinated sequence of primary and secondary IGK gene rearrangement, IGK deletion, and IGL gene rearrangement","volume":"174","author":"Klein","year":"2005","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib25","doi-asserted-by":"publisher","first-page":"7435","DOI":"10.1073\/pnas.130182597","article-title":"B cell receptor expression level determines the fate of developing B lymphocytes: receptor editing versus selection","volume":"97","author":"Kouskoff","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072603182181900_bib26","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s12026-007-8008-7","article-title":"Understanding B-cell tolerance through the use of immunoglobulin transgenic models","volume":"40","author":"Kumar","year":"2008","journal-title":"Immunol. Res."},{"key":"2023072603182181900_bib27","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1002\/j.1460-2075.1993.tb06189.x","article-title":"Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections","volume":"12","author":"K\u00fcppers","year":"1993","journal-title":"EMBO J."},{"key":"2023072603182181900_bib28","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.clim.2011.04.002","article-title":"Generation of hematopoietic humanized mice in the newborn BALB\/c-Rag2nullIl2r\u03b3null mouse model: a multivariable optimization approach","volume":"140","author":"Lang","year":"2011","journal-title":"Clin. Immunol."},{"key":"2023072603182181900_bib29","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.4049\/jimmunol.1202810","article-title":"Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation","volume":"190","author":"Lang","year":"2013","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib30","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.4049\/jimmunol.173.6.3878","article-title":"Unraveling the consecutive recombination events in the human IGK locus","volume":"173","author":"Langerak","year":"2004","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib31","doi-asserted-by":"publisher","first-page":"6322","DOI":"10.4049\/jimmunol.165.11.6322","article-title":"The V\u03bbJ\u03bb repertoire in human fetal spleen: Evidence for positive selection and extensive receptor editing","volume":"165","author":"Lee","year":"2000","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib32","first-page":"65","article-title":"Experimental model for the study of the human immune system: Production and monitoring of \u201chuman immune system\u201d Rag2\u2212\/\u2212\u03b3c\u2212\/\u2212 mice","volume":"415","author":"Legrand","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"2023072603182181900_bib33","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.chom.2009.06.006","article-title":"Humanized mice for modeling human infectious disease: challenges, progress, and outlook","volume":"6","author":"Legrand","year":"2009","journal-title":"Cell Host Microbe."},{"key":"2023072603182181900_bib34","doi-asserted-by":"publisher","first-page":"5067","DOI":"10.4049\/jimmunol.175.8.5067","article-title":"Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens","volume":"175","author":"Liu","year":"2005","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib35","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1038\/ni1009-1039","article-title":"Renaissance for mouse models of human hematopoiesis and immunobiology","volume":"10","author":"Manz","year":"2009","journal-title":"Nat. Immunol."},{"key":"2023072603182181900_bib36","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S1074-7613(00)80157-0","article-title":"Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk","volume":"12","author":"Martin","year":"2000","journal-title":"Immunity."},{"key":"2023072603182181900_bib37","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1189\/jlb.0113048","article-title":"The human fetal lymphocyte lineage: identification by CD27 and LIN28B expression in B cell progenitors","volume":"94","author":"McWilliams","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"2023072603182181900_bib38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.2011.06347.x","article-title":"The establishment of early B cell tolerance in humans: lessons from primary immunodeficiency diseases","volume":"1246","author":"Meffre","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023072603182181900_bib39","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.coi.2008.09.001","article-title":"B-cell tolerance checkpoints in health and autoimmunity","volume":"20","author":"Meffre","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"2023072603182181900_bib40","doi-asserted-by":"publisher","first-page":"9267","DOI":"10.1073\/pnas.94.17.9267","article-title":"Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest","volume":"94","author":"Melamed","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072603182181900_bib41","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0092-8674(00)80912-5","article-title":"Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection","volume":"92","author":"Melamed","year":"1998","journal-title":"Cell."},{"key":"2023072603182181900_bib42","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1084\/jem.20040920","article-title":"Bruton\u2019s tyrosine kinase is essential for human B cell tolerance","volume":"200","author":"Ng","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib43","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1084\/jem.20102265","article-title":"Liver-expressed Ig\u03ba superantigen induces tolerance of polyclonal B cells by clonal deletion not \u03ba to \u03bb receptor editing","volume":"208","author":"Ota","year":"2011","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib44","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1084\/jem.20082053","article-title":"RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes","volume":"205","author":"Panigrahi","year":"2008","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib45","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.coi.2006.01.005","article-title":"Receptor editing for better or for worse","volume":"18","author":"Pelanda","year":"2006","journal-title":"Curr. Opin. Immunol."},{"key":"2023072603182181900_bib46","doi-asserted-by":"publisher","first-page":"a007146","DOI":"10.1101\/cshperspect.a007146","article-title":"Central B-cell tolerance: where selection begins","volume":"4","author":"Pelanda","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2023072603182181900_bib47","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S1074-7613(00)80395-7","article-title":"Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification","volume":"7","author":"Pelanda","year":"1997","journal-title":"Immunity."},{"key":"2023072603182181900_bib48","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.4049\/jimmunol.166.4.2412","article-title":"Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds","volume":"166","author":"Qian","year":"2001","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib49","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.molimm.2012.03.028","article-title":"B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients","volume":"51","author":"Schoettler","year":"2012","journal-title":"Mol. Immunol."},{"key":"2023072603182181900_bib50","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.immuni.2007.12.004","article-title":"Sites and stages of autoreactive B cell activation and regulation","volume":"28","author":"Shlomchik","year":"2008","journal-title":"Immunity."},{"key":"2023072603182181900_bib51","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nri3311","article-title":"Humanized mice for immune system investigation: progress, promise and challenges","volume":"12","author":"Shultz","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"2023072603182181900_bib52","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/316260a0","article-title":"A uniform deleting element mediates the loss of \u03ba genes in human B cells","volume":"316","author":"Siminovitch","year":"1985","journal-title":"Nature."},{"key":"2023072603182181900_bib53","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/j.0105-2896.2009.00858.x","article-title":"Role of HLA class II genes in susceptibility\/resistance to inflammatory arthritis: studies with humanized mice","volume":"233","author":"Taneja","year":"2010","journal-title":"Immunol. Rev."},{"key":"2023072603182181900_bib54","doi-asserted-by":"publisher","first-page":"E2797","DOI":"10.1073\/pnas.1402159111","article-title":"Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies","volume":"111","author":"Teodorovic","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072603182181900_bib55","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1084\/jem.177.4.1009","article-title":"Receptor editing in self-reactive bone marrow B cells","volume":"177","author":"Tiegs","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib56","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jim.2007.09.017","article-title":"Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning","volume":"329","author":"Tiller","year":"2008","journal-title":"J. Immunol. Methods."},{"key":"2023072603182181900_bib57","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.1093933","article-title":"Development of a human adaptive immune system in cord blood cell-transplanted mice","volume":"304","author":"Traggiai","year":"2004","journal-title":"Science."},{"key":"2023072603182181900_bib58","doi-asserted-by":"publisher","first-page":"6796","DOI":"10.4049\/jimmunol.165.12.6796","article-title":"Ig light chain receptor editing in anergic B cells","volume":"165","author":"Tze","year":"2000","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib59","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.immuni.2005.03.006","article-title":"A role for nuclear factor kappa B\/rel transcription factors in the regulation of the recombinase activator genes","volume":"22","author":"Verkoczy","year":"2005","journal-title":"Immunity."},{"key":"2023072603182181900_bib60","doi-asserted-by":"publisher","first-page":"6332","DOI":"10.4049\/jimmunol.178.10.6332","article-title":"Basal B cell receptor-directed phosphatidylinositol 3-kinase signaling turns off RAGs and promotes B cell-positive selection","volume":"178","author":"Verkoczy","year":"2007","journal-title":"J. Immunol."},{"key":"2023072603182181900_bib61","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jim.2014.06.010","article-title":"Critical assessment of human antibody generation in humanized mouse models","volume":"410","author":"Villaudy","year":"2014","journal-title":"J. Immunol. Methods."},{"key":"2023072603182181900_bib62","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1126\/science.1086907","article-title":"Predominant autoantibody production by early human B cell precursors","volume":"301","author":"Wardemann","year":"2003","journal-title":"Science."},{"key":"2023072603182181900_bib63","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1084\/jem.20040818","article-title":"Human autoantibody silencing by immunoglobulin light chains","volume":"200","author":"Wardemann","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023072603182181900_bib64","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.immuni.2005.08.007","article-title":"Evidence of marginal-zone B cell-positive selection in spleen","volume":"23","author":"Wen","year":"2005","journal-title":"Immunity."},{"key":"2023072603182181900_bib65","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1126\/science.1216557","article-title":"Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis","volume":"335","author":"Yuan","year":"2012","journal-title":"Science."},{"key":"2023072603182181900_bib66","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1084\/jem.20141510","article-title":"Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a","volume":"212","author":"Zhou","year":"2015","journal-title":"J. Exp. Med."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/213\/1\/93\/1754920\/jem_20151039.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/213\/1\/93\/1754920\/jem_20151039.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T23:18:56Z","timestamp":1690327136000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/213\/1\/93\/41882\/Receptor-editing-and-genetic-variability-in-human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,22]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1,11]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20151039","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726034926.793513088","asserted-by":"object"}]},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,22]]}}}