| First Author | Haas C | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 8 | Pages | 3713-8 |
| PubMed ID | 9558072 | Mgi Jnum | J:111168 |
| Mgi Id | MGI:3653151 | Doi | 10.4049/jimmunol.160.8.3713 |
| Citation | Haas C, et al. (1998) IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice. J Immunol 160(8):3713-8 |
| abstractText | (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 inactivation of IFN-gamma signaling on autoAb production. |
