PMID: 9558072Apr 29, 1998Paper

IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice

The Journal of Immunology : Official Journal of the American Association of Immunologists
C HaasM Le Hir

Abstract

(NZB x NZW)F1 female (BW) mice spontaneously develop an autoimmune disease, characterized by the production of autoantibodies (autoAbs) and glomerulonephritis, which can be delayed by neutralizing IFN-gamma Abs and accelerated by IFN-gamma injections. To define the role of IFN-gamma in the pathogenesis of glomerulonephritis, we established a population of BW mice deficient in IFN-gammaR (BWgammaR[-/-]) by repeated crossing; these mice were compared with BWgammaR(+/+) and +/- littermates. Of the BWgammaR(+/+) and +/- mice, 50% showed immune complex glomerulonephritis with heavy proteinuria at 8 mo of age, while only 10% of the BWgammaR(-/-) mice were affected at 14 mo. The serum concentration of anti-dsDNA and anti-histone Abs was dramatically reduced in BWgammaR(-/-) mice. The role of IFN-gamma in promoting class switch to IgG2a and IgG3 could not fully account for the impaired production of anti-dsDNA in BWgammaR(-/-) animals since, IgM and IgG1 levels were also reduced. There was a high incidence of B cell lymphoma in the BWgammaR(-/-) mice, which might be related to the suppression of autoAb production. Thus, the absence of glomerulonephritis in BWgammaR(-/-) mice is likely due to a dramatic yet unexplained effect of the ina...Continue Reading

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