Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice
2014
The IgM-
Fc receptor(FcμR) 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 FcμR(−) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(−) 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 FcμR(−) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into
plasma cellsin the absence of FcμR, 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 FcμR(−) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant
plasma cellswith intra-
cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of
renal pathologyand function and survival were all indistinguishable between FcμR(−) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into
plasma cellsin B6.MRL Fas lpr/lpr mice.
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