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.


CONCLUSIONS
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.
Matsumoto
Keiko
K
Graduate School of Medicine, Chiba University, Chiba, Japan.
Watanabe
Norihiko
N
Akikusa
Bunshiro
B
Kurasawa
Kazuhiro
K
Matsumura
Ryutaro
R
Saito
Yasushi
Y
Iwamoto
Itsuo
I
Saito
Takashi
T
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D001183:Arthus Reaction / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D015996:Survival Rate; D014657:Vasculitis / Q000276:immunology / Q000401:mortality / Q000503:physiopathology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017452:Receptors, IgG