RT Journal Article
SR Electronic
T1 Inhibition of B Cell Death Causes the Development of an IgA Nephropathy in (New Zealand White × C57BL/6)F<sub>1</sub>-<em>bcl-2</em> Transgenic Mice
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 7177
OP 7185
DO 10.4049/jimmunol.172.11.7177
VO 172
IS 11
A1 Marquina, Regina
A1 Díez, Miguel A.
A1 López-Hoyos, Marcos
A1 Buelta, Luis
A1 Kuroki, Aki
A1 Kikuchi, Shuichi
A1 Villegas, Juan
A1 Pihlgren, Maria
A1 Siegrist, Claire-Anne
A1 Arias, Manuel
A1 Izui, Shozo
A1 Merino, Jesús
A1 Merino, Ramón
YR 2004
UL http://www.jimmunol.org/content/172/11/7177.abstract
AB 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) × C57BL/6)F1 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 × C57BL/6)F1-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 × C57BL/6)F1-hbcl-2 Tg mice provide a new experimental model for this form of glomerulonephritis.