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

Lopez-Hoyos, Marcos
Fossati-Jimack, Liliane
Merino, Jesus
Merino, Ramon
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Published in European Journal of Immunology. 2004, vol. 34, no. 4, p. 1077-1084
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.
Keywords AnimalsAntibodies, Antinuclear/*biosynthesis/bloodApoptosis/physiologyArthritis, Rheumatoid/immunologyB-Lymphocytes/*immunology/metabolismChimeraDisease Models, AnimalEnzyme-Linked Immunosorbent AssayGlomerulonephritis/etiology/immunology/pathologyHumansImmunoglobulin G/biosynthesis/bloodLupus Erythematosus, Systemic/complications/immunology/*physiopathologyMaleMiceMutationProto-Oncogene Proteins c-bcl-2/*biosynthesis/geneticsRheumatoid Factor/*immunology
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PMID: 15048718
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