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We had previously generated and characterized knock\u2010in mice expressing a germline\u2010encoded, CII\u2010specific IgH (B10Q.ACB), which demonstrated positive selection of self\u2010reactive B cells. Here, we show that despite the spontaneous production of CII\u2010specific autoantibodies, B10Q.ACB mice are protected from collagen\u2010induced arthritis. Introducing a mutation in the <jats:italic>Ncf1<\/jats:italic> gene, leading to ROS deficiency, breaks this strong arthritis resistance. Disease development in <jats:italic>Ncf1<\/jats:italic>\u2010mutated B10Q.ACB mice is associated with an enhanced germinal center formation but without somatic mutations of the auto\u2010reactive B cells, increased T\u2010cell responses and intramolecular epitope\u2010spreading. Thus, ROS\u2010mediated B\u2010cell tolerance to a self\u2010antigen could operate by limiting the expansion of the auto\u2010reactive B\u2010cell repertoire, which has important implications for the understanding of epitope spreading phenomena in rheumatoid arthritis and other autoimmune diseases.<\/jats:p>","DOI":"10.1002\/eji.201545518","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T05:16:29Z","timestamp":1432012589000},"page":"2243-2251","source":"Crossref","is-referenced-by-count":23,"title":["B\u2010cell epitope spreading and inflammation in a mouse model of arthritis is associated with a deficiency in reactive oxygen species production"],"prefix":"10.1002","volume":"45","author":[{"given":"Ia","family":"Khmaladze","sequence":"first","affiliation":[{"name":"Medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"},{"name":"Unit of Dermatology, Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Saxena","sequence":"additional","affiliation":[{"name":"Medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kutty Selva","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"},{"name":"Unit of Medical Inflammation Research Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280503"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.124537"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035296"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115164"},{"key":"e_1_2_7_7_1","first-page":"2090","article-title":"IgG subclasses of antibodies to type II collagen in rheumatoid arthritis differ from those in systemic lupus erythematosus and other connective tissue diseases","volume":"24","author":"Cook A. 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