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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3492-3496
Number of pages5
JournalJournal of Immunology
Volume201
Issue number12
DOIs
Publication statusPublished - Dec 15 2018

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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