Enforced Bcl-2 expression in B lymphocytes induces rheumatoid factor and anti-DNA production, but the Yaa mutation promotes only anti-DNA production

Eur J Immunol. 2004 Apr;34(4):1077-84. doi: 10.1002/eji.200424859.


The presence of rheumatoid factors (RF) is a characteristic feature of patients with rheumatoid arthritis, but not systemic lupus erythematosus. In this study, we have explored the role of the anti-apoptotic Bcl-2 protein and the Y-linked autoimmune acceleration (Yaa) mutation in the production of IgG RF in comparison with IgG anti-DNA autoimmune responses. Analysis in C57BL/6 mice, in their F1 hybrids with lupus-prone NZW mice, and in bone marrow chimeras containing mixtures of C57BL/6 bcl-2-transgenic and BXSB non-transgenic cells demonstrated that an enforced Bcl-2 expression in B cells promoted the induction of IgG anti-DNA production in these mice, while significant IgG RF responses were observed only in mice developing high levels of gp70-anti-gp70 immune complexes and lethal glomerulonephritis. Moreover, in contrast to a synergistic interaction between the Yaa mutation and Bcl-2 overexpression on IgG anti-DNA production, the Yaa mutation failed to enhance the production of IgG RF induced in bcl-2-transgenic mice. Our results reveal that defects in the regulation of B cell apoptosis play a critical role in the production of IgG RF, and that the Yaa mutation differentially modulates RF and anti-DNA autoimmune responses, likely related to the nature of autoantigens involved in each autoimmune response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / blood
  • Apoptosis / physiology
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Chimera
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Glomerulonephritis / etiology
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Mice
  • Mutation
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Rheumatoid Factor / immunology*


  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Proto-Oncogene Proteins c-bcl-2
  • Rheumatoid Factor