{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:14:22Z","timestamp":1773306862815,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"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":[[2018,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Generation of neoantigens by citrullination is implicated in the production of anti\u2013citrullinated protein Abs in rheumatoid arthritis, but citrullination is also a physiological process. To verify whether citrullin-specific B cells are immunologically ignorant or tolerant in normal conditions, transgenic (Tg) mice expressing IgM with the V region of an anti\u2013cyclic citrullinated peptide (CCP) mAb cloned from a rheumatoid arthritis patient were generated. CCP-specific B cells developed in the anti-CCP IgM Tg mice with an alteration of bone marrow B cell fractions, and the number of mature B cells decreased compared with wild-type or the control anti\u2013influenza nucleoprotein\u2013specific IgM Tg mice. In addition, B cells in anti-CCP IgM Tg mice are functionally anergic. Thus, tolerance is induced in CCP-specific B cells in vivo, suggesting that the immune systems are naturally exposed to citrullinated Ags, and anti-CCP Ab production requires additional steps beyond the generation of neoantigens by citrullination.<\/jats:p>","DOI":"10.4049\/jimmunol.1800826","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T15:45:14Z","timestamp":1542037514000},"page":"3492-3496","source":"Crossref","is-referenced-by-count":16,"title":["Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide\u2013Specific Antigen Receptor Are Tolerized in Normal Conditions"],"prefix":"10.1093","volume":"201","author":[{"given":"Hisakata","family":"Yamada","sequence":"first","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 ,","place":["Japan"]},{"name":"Department of Orthopaedic Surgery, Kyushu University , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-452X","authenticated-orcid":false,"given":"Tatsuhiko","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama 930-0194 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama 930-0194 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Kyushu University , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuharu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Kyushu University , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Muraguchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama 930-0194 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunobu","family":"Yoshikai","sequence":"additional","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,15]]},"reference":[{"key":"2025030417580101100_r1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3","article-title":"The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide","volume":"43","author":"Schellekens","year":"2000","journal-title":"Arthritis Rheum."},{"key":"2025030417580101100_r2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/art.20018","article-title":"Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors","volume":"50","author":"Nielen","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2025030417580101100_r3","doi-asserted-by":"crossref","first-page":"700","DOI":"10.2174\/1389450116666150202160954","article-title":"Protein arginine deiminases and associated citrullination: physiological functions and diseases associated with dysregulation","volume":"16","author":"Witalison","year":"2015","journal-title":"Curr. 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