| First Author | Yamada H | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 12 | Pages | 3492-3496 |
| PubMed ID | 30420436 | Mgi Jnum | J:268251 |
| Mgi Id | MGI:6269198 | Doi | 10.4049/jimmunol.1800826 |
| Citation | Yamada H, et al. (2018) Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide-Specific Antigen Receptor Are Tolerized in Normal Conditions. J Immunol 201(12):3492-3496 |
| abstractText | 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. |
