{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:04:23Z","timestamp":1791180263143,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>AM14 rheumatoid factor (RF) B cells in the MRL\/lpr mice are activated by dual BCR and TLR7\/9 ligation and differentiate into plasmablasts via an extrafollicular (EF) route. It was not known whether this mechanism of activation of RF B cells applied to other lupus-prone mouse models. We investigated the mechanisms by which RF B cells break tolerance in the NZM2410-derived B6.Sle1.Sle2.Sle3 (TC) strain in comparison with C57BL\/6 (B6) controls, each expressing the AM14 H chain transgene in the presence or absence of the IgG2aa autoantigen. The TC, but not B6, genetic background promotes the differentiation of RF B cells into Ab-forming cells (AFCs) in the presence of the autoantigen. Activated RF B cells preferentially differentiated into plasmablasts in EF zones. Contrary to the MRL\/lpr strain, TC RF B cells were also located within germinal centers, but only the formation of EF foci was positively correlated with the production of RF AFCs. Immunization of young TC.AM14 H chain transgenic mice with IgG2aa anti-chromatin immune complexes (ICs) activated RF B cells in a BCR- and TLR9-dependent manner. However, these IC immunizations did not result in the production of RF AFCs. These results show that RF B cells break tolerance with the same general mechanisms in the TC and the MRL\/lpr lupus-prone genetic backgrounds, namely the dual activation of the BCR and TLR9 pathways. There are also distinct differences, such as the presence of RF B cells in GCs and the requirement of chronic IgG2aa anti-chromatin ICs for full differentiation of RF AFCs.<\/jats:p>","DOI":"10.4049\/jimmunol.1303000","type":"journal-article","created":{"date-parts":[[2014,7,12]],"date-time":"2014-07-12T03:00:11Z","timestamp":1405134011000},"page":"1609-1621","source":"Crossref","is-referenced-by-count":40,"title":["Activation of Rheumatoid Factor\u2013Specific B Cells Is Antigen Dependent and Occurs Preferentially Outside of Germinal Centers in the Lupus-Prone NZM2410 Mouse Model"],"prefix":"10.1093","volume":"193","author":[{"given":"Allison","family":"Sang","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Cullen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,15]]},"reference":[{"key":"2025030707294042800_r1","doi-asserted-by":"crossref","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":"2025030707294042800_r2","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1093\/intimm\/5.10.1329","article-title":"A rheumatoid factor transgenic mouse model of autoantibody regulation","volume":"5","author":"Shlomchik","year":"1993","journal-title":"Int. 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