Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice

Objective. To determine the role of Fc receptors (FcR), which play crucial roles in antibody and immune complex-mediated inflammation and autoimmunity, including glomerulonephritis (GN), in the development of autoimmune GN and vasculitis in MRL/lpr mice, one of the most widely used lupus-prone mouse models. Methods. FcRgamma(-/-) MRL/lpr mice were generated by backcrossing for 8 generations. The development of GN and vasculitis of various sized vessels was analyzed histopathologically in the kidney, lung, and skin. Autoantibody and immune complex levels were determined biochemically at 16-24 weeks of age and compared with the findings in FcRgamma(+) MRL/lpr mice. The lifespan of the mice was also recorded. Results. Diffuse proliferative GN, with deposition of IgG and C3, developed in both FcRgamma(-/-) and FcRgamma(+) MRL/lpr mice. There was no difference in the survival rate and degree of proteinuria between FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. Regardless of the level of FcR expression, there were no significant differences in the levels of serum IgG, anti-DNA antibody, or circulating immune complexes between the two types of mice. Necrotizing vasculitis in medium-sized arteries of the kidneys and lungs as well as small-vessel vasculitis in the skin was observed in both in FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. In contrast, the Arthus reaction was induced in FcRgamma(+) MRL/lpr mice, but not in FcRgamma(-/-) MRL/lpr mice. Conclusion. Unlike (NZB X NZW)F-1, the other strain of lupus-prone mice that develops GN in an FcR-dependent manner, the development of autoimmune GN and vasculitis in MRL/lpr mice was FcR-independent, implying heterogeneity of the contribution of FcR to the development of autoimmune disease.