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
; 34(4): 1077-84, 2004 Apr.
Article
em En
| MEDLINE
| ID: mdl-15048718
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Reumatoide
/
Linfócitos B
/
Anticorpos Antinucleares
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
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