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Scientific article
English

Defects in the regulation of B cell apoptosis are required for the production of citrullinated peptide autoantibodies in mice

Published inArthritis and rheumatism, vol. 48, no. 8, p. 2353-2361
Publication date2003
Abstract

OBJECTIVE: Protein deimination, a process to modify arginine residues to citrulline by the addition of a neutral oxygen group, is associated with apoptosis. The presence of autoantibodies recognizing citrullinated peptides is highly specific to rheumatoid arthritis (RA) and is therefore a useful marker for the early diagnosis of RA. In this study, we explored whether anti-cyclic citrullinated peptide (anti-CCP) autoantibodies are produced in several experimental models of autoimmune diseases in mice. METHODS: The levels of anti-CCP autoantibodies were analyzed by enzyme-linked immunosorbent assay in several lupus-prone strains of mice, in animals with type II collagen (CII)-induced arthritis, and after induction of neonatal tolerance to alloantigens. RESULTS: We observed the production of these autoantibodies in 2 different lupus-prone mice, MRL-lpr/lpr and (NZW x B6)F(1)-hbcl-2 transgenic mice, characterized by the presence of abnormalities in the regulation of B cell apoptosis. Other genetic defects, determining autoimmune susceptibility, present in MRL and NZW mice were additionally required for anti-CCP autoantibody production. The induction of autoantibodies in normal BALB/c mice injected at birth with semiallogeneic spleen cells from (BALB/c x B6)F(1)-hbcl-2 transgenic mice suggested that these additional autoimmune defects may be related, at least in part, to the establishment of abnormal interactions between T cells and B cells. In addition, anti-CCP autoantibodies were not produced in the course of CII-induced arthritis, an experimental model of RA in mice. CONCLUSION: Our study provides evidence for the association between defects in the regulatory cell death machinery of B lymphocytes and the production of certain autoantibody specificities.

Keywords
  • Animals
  • Apoptosis/ immunology
  • Arthritis, Rheumatoid/ immunology
  • Autoantibodies/ immunology/metabolism
  • B-Lymphocytes/ cytology/ immunology
  • Cell Communication/immunology
  • Citrulline/ immunology
  • Gene Expression/immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred MRL lpr
  • Mice, Inbred NZB
  • Mice, Transgenic
  • Peptides/immunology
  • Proto-Oncogene Proteins c-bcl-2/genetics
  • Species Specificity
  • T-Lymphocytes/cytology/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
LOPEZ-HOYOS, Marcos et al. Defects in the regulation of B cell apoptosis are required for the production of citrullinated peptide autoantibodies in mice. In: Arthritis and rheumatism, 2003, vol. 48, n° 8, p. 2353–2361. doi: 10.1002/art.11107
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ISSN of the journal0004-3591
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