Cutting edge: B cells expressing cyclic citrullinated peptide-specific antigen receptor are tolerized in normal conditions

Hisakata Yamada*, Tatsuhiko Ozawa, Hiroyuki Kishi, Seiji Okada, Yasuharu Nakashima, Atsushi Muraguchi, Yasunobu Yoshikai

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

12 被引用数 (Scopus)

抄録

Generation of neoantigens by citrullination is implicated in the production of anti-citrullinated 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-cyclic 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-influenza nucleoprotein-specific 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.

本文言語英語
ページ(範囲)3492-3496
ページ数5
ジャーナルJournal of Immunology
201
12
DOI
出版ステータス出版済み - 2018/12/15

ASJC Scopus 主題領域

  • 免疫アレルギー学
  • 免疫学

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