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

C Haas, B Ryffel, M Le Hir - The Journal of Immunology, 1998 - journals.aai.org
C Haas, B Ryffel, M Le Hir
The Journal of Immunology, 1998journals.aai.org
Abstract (NZB× NZW) F 1 female (BW) mice spontaneously develop an autoimmune
disease, characterized by the production of autoantibodies (autoAbs) and
glomerulonephritis, which can be delayed by neutralizing IFN-γ Abs and accelerated by IFN-
γ injections. To define the role of IFN-γ in the pathogenesis of glomerulonephritis, we
established a population of BW mice deficient in IFN-γR (BWγR−/−) by repeated crossing;
these mice were compared with BWγR+/+ and+/− littermates. Of the BWγR+/+ and+/− mice …
Abstract
(NZB× NZW) F 1 female (BW) mice spontaneously develop an autoimmune disease, characterized by the production of autoantibodies (autoAbs) and glomerulonephritis, which can be delayed by neutralizing IFN-γ Abs and accelerated by IFN-γ injections. To define the role of IFN-γ in the pathogenesis of glomerulonephritis, we established a population of BW mice deficient in IFN-γR (BWγR−/−) by repeated crossing; these mice were compared with BWγR+/+ and+/− littermates. Of the BWγR+/+ and+/− mice, 50% showed immune complex glomerulonephritis with heavy proteinuria at 8 mo of age, while only 10% of the BWγR−/− mice were affected at 14 mo. The serum concentration of anti-dsDNA and anti-histone Abs was dramatically reduced in BWγR−/− mice. The role of IFN-γ in promoting class switch to IgG2a and IgG3 could not fully account for the impaired production of anti-dsDNA in BWγR−/− animals since, IgM and IgG1 levels were also reduced. There was a high incidence of B cell lymphoma in the BWγR−/− mice, which might be related to the suppression of autoAb production. Thus, the absence of glomerulonephritis in BWγR−/− mice is likely due to a dramatic yet unexplained effect of the inactivation of IFN-γ signaling on autoAb production.
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