PT - JOURNAL ARTICLE AU - Haas, Cordula AU - Ryffel, Bernhard AU - Le Hir, Michel TI - IFN-γ Receptor Deletion Prevents Autoantibody Production and Glomerulonephritis in Lupus-Prone (NZB × NZW)F<sub>1</sub> Mice DP - 1998 Apr 15 TA - The Journal of Immunology PG - 3713--3718 VI - 160 IP - 8 4099 - http://www.jimmunol.org/content/160/8/3713.short 4100 - http://www.jimmunol.org/content/160/8/3713.full SO - J. Immunol.1998 Apr 15; 160 AB - (NZB × 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-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.