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

2 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

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Antigen Receptors
B-Lymphocytes
Transgenic Mice
Immunoglobulin M
Rheumatoid Arthritis
Physiological Phenomena
Nucleoproteins
Bone Marrow Cells
Human Influenza
cyclic citrullinated peptide
Immune System
Cell Count
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Cutting edge : B cells expressing cyclic citrullinated peptide-specific antigen receptor are tolerized in normal conditions. / Yamada, Hisakata; Ozawa, Tatsuhiko; Kishi, Hiroyuki; Okada, Seiji; Nakashima, Yasuharu; Muraguchi, Atsushi; Yoshikai, Yasunobu.

In: Journal of Immunology, Vol. 201, No. 12, 15.12.2018, p. 3492-3496.

Research output: Contribution to journalArticle

Yamada, Hisakata ; Ozawa, Tatsuhiko ; Kishi, Hiroyuki ; Okada, Seiji ; Nakashima, Yasuharu ; Muraguchi, Atsushi ; Yoshikai, Yasunobu. / Cutting edge : B cells expressing cyclic citrullinated peptide-specific antigen receptor are tolerized in normal conditions. In: Journal of Immunology. 2018 ; Vol. 201, No. 12. pp. 3492-3496.
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