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Title

Inhibition of B cell death causes the development of an IgA nephropathy in (New Zealand white x C57BL/6)F(1)-bcl-2 transgenic mice

Authors
Marquina, Regina
Diez, M. A.
Lopez-Hoyos, Marcos
Buelta, Luis
Villegas, Juan
Pihlgren, Maria
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Published in Journal of Immunology. 2004, vol. 172, no. 11, p. 7177-7185
Abstract Little is known about the pathogenic mechanisms of IgA nephropathy, despite being the most prevalent form of glomerulonephritis in humans. We report in this study that in (New Zealand White (NZW) x C57BL/6)F(1) mice predisposed to autoimmune diseases, the expression of a human bcl-2 (hbcl-2) transgene in B cells promotes a CD4-dependent lupus-like syndrome characterized by IgG and IgA hypergammaglobulinemia, autoantibody production, and the development of a fatal glomerulonephritis. Histopathological analysis of glomerular lesions reveals that the glomerulonephritis observed in these animals resembles that of human IgA nephropathy. The overexpression of Bcl-2 in B cells selectively enhances systemic IgA immune responses to T-dependent Ags. Significantly, serum IgA purified from (NZW x C57BL/6)F(1)-hbcl-2 transgenic mice, but not from nontransgenic littermates, shows reduced levels of galactosylation and sialylation and an increased ability to deposit in the glomeruli, as observed in human patients with IgA nephropathy. Our results indicate that defects in the regulation of B lymphocyte survival associated with aberrant IgA glycosylation may be critically involved in the pathogenesis of IgA nephropathy, and that (NZW x C57BL/6)F(1)-hbcl-2 Tg mice provide a new experimental model for this form of glomerulonephritis.
Keywords Animals*ApoptosisB-Lymphocytes/*physiologyFemaleGlomerulonephritisIGA/*etiologyGlycosylationImmunoglobulin A/metabolismLupus ErythematosusSystemic/etiologyMiceInbred C57BLInbred NZBTransgenicProto-Oncogene Proteins c-bcl-2/*physiology
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PMID: 15153542
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Other version: http://www.jimmunol.org/cgi/reprint/172/11/7177.pdf
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Research group Centre de Vaccinologie et d'Immunologie néonatale (177)
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MARQUINA, Regina et al. Inhibition of B cell death causes the development of an IgA nephropathy in (New Zealand white x C57BL/6)F(1)-bcl-2 transgenic mice. In: Journal of Immunology, 2004, vol. 172, n° 11, p. 7177-7185. https://archive-ouverte.unige.ch/unige:11442

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Deposited on : 2010-08-27

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