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Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide-Specific Antigen Receptor Are Tolerized in Normal Conditions.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Dec 15; Vol. 201 (12), pp. 3492-3496. Date of Electronic Publication: 2018 Nov 12. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antibodies, Monoclonal genetics
Cells, Cultured
Clonal Anergy
Humans
Immune Tolerance
Immunoglobulin M genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Protein Engineering
Receptors, Antigen, B-Cell genetics
Arthritis, Rheumatoid immunology
B-Lymphocytes immunology
Immunoglobulin M metabolism
Peptides, Cyclic immunology
Receptors, Antigen, B-Cell metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 201
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 30420436
- Full Text :
- https://doi.org/10.4049/jimmunol.1800826