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Pathogenic autoreactive B cells are not negatively selected toward matrix protein collagen II.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Nov 01; Vol. 187 (9), pp. 4451-8. Date of Electronic Publication: 2011 Sep 21. - Publication Year :
- 2011
-
Abstract
- We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for other epitopes. In addition, Abs from CII-specific hybridomas generated from ACB mice induced arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed a lack of somatic mutations in autoreactive B cells. The ACB model provides the first possibility, to our knowledge, to study B cell tolerance to a matrix protein, and the observations made in the study could not be predicted from previous models. B cell-reactive epitopes on CII are largely shared between human RA and rodent CII-induced arthritis; this study, therefore, has important implications for further understanding of pathological processes in autoimmune diseases like RA.
- Subjects :
- Animals
Arthritis, Experimental metabolism
Arthritis, Experimental pathology
Arthritis, Rheumatoid immunology
Arthritis, Rheumatoid metabolism
Arthritis, Rheumatoid pathology
Autoantibodies metabolism
B-Lymphocyte Subsets metabolism
Binding Sites, Antibody
Disease Models, Animal
Epitopes, B-Lymphocyte immunology
Extracellular Matrix Proteins metabolism
Gene Knock-In Techniques
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Spleen cytology
Spleen immunology
Arthritis, Experimental immunology
B-Lymphocyte Subsets immunology
B-Lymphocyte Subsets pathology
Collagen Type II immunology
Extracellular Matrix Proteins immunology
Immune Tolerance
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 187
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21940677
- Full Text :
- https://doi.org/10.4049/jimmunol.1101378