Scientific article

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

Published inThe Journal of immunology, vol. 172, no. 11, p. 7177-7185
Publication date2004

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.

  • Animals
  • *Apoptosis
  • B-Lymphocytes/*physiology
  • Female
  • Glomerulonephritis
  • IGA/*etiology
  • Glycosylation
  • Immunoglobulin A/metabolism
  • Lupus Erythematosus
  • Systemic/etiology
  • Mice
  • Inbred C57BL
  • Inbred NZB
  • Transgenic
  • Proto-Oncogene Proteins c-bcl-2/*physiology
Citation (ISO format)
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: The Journal of immunology, 2004, vol. 172, n° 11, p. 7177–7185. doi: 10.4049/jimmunol.172.11.7177
Updates (1)
ISSN of the journal0022-1767

Technical informations

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