Enhanced Auto-Antibody Production And Mott Cell Formation In Fc Mu R-Deficient Autoimmune Mice

The IgM-Fc receptor (Fc mu R) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6. MRL Fas(lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in Fc mu R(-) B6/lpr than Fc mu R(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in Fc mu R(+) B6/lpr mice, were reduced to normal B6 levels in Fc mu R(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in Fc mu R(-) B6/lpr mice compared with either Fc mu R(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of Fc mu R, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of Fc mu R(-) mice compared with Fc mu R(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of Fc mu R. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between Fc mu R(-) and Fc mu R(+) B6/lpr mice. Collectively, these findings suggest that Fc mu R plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6. MRL Fas(lpr/lpr) mice.