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The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell\u2013derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell\u2013derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-\u03b3, consistent with the critical roles for B cell\u2013intrinsic IFN-\u03b3 receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.<\/jats:p>","DOI":"10.1084\/jem.20170580","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T10:10:17Z","timestamp":1505211017000},"page":"3207-3217","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":269,"title":["B cell\u2013derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity"],"prefix":"10.1084","volume":"214","author":[{"given":"Tanvi","family":"Arkatkar","sequence":"first","affiliation":[{"name":"Seattle Children's Research Institute, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-3659","authenticated-orcid":true,"given":"Samuel W.","family":"Du","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3250-8258","authenticated-orcid":true,"given":"Holly M.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0359-6116","authenticated-orcid":true,"given":"Elizabeth M.","family":"Dam","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute, Seattle, WA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-5216","authenticated-orcid":true,"given":"Baidong","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-1885","authenticated-orcid":true,"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute, Seattle, WA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0810-1776","authenticated-orcid":true,"given":"David J.","family":"Rawlings","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Seattle, WA 1"},{"name":"Department of Immunology, University of Washington School of Medicine, Seattle, WA 3"},{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun W.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Seattle, WA 1"},{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,9,12]]},"reference":[{"key":"2023072603334472600_bib1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nri1786","article-title":"Lymphoid neogenesis in chronic inflammatory diseases","volume":"6","author":"Aloisi","year":"2006","journal-title":"Nat. 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