Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice. (3rd July 2014)

• Record Type: Journal Article
• Authors: Honjo, Kazuhito; Kubagawa, Yoshiki; Suzuki, Yusuke; Takagi, Miyuki; Ohno, Hiroshi; Bucy, R. Pat; Izui, Shozo; Kubagawa, Hiromi
• Is Part Of: International immunology. Volume 26:Number 12(2014:Dec.)
• Page Start: 659
• Page End: 672
• Publication Date: 2014-07-03
• Subjects: auto-antibody -- FcμR -- IgM -- marginal zone B cells -- Mott cells; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxu070
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : Characterization of FcμR deficiency in lupus-prone mice Abstract: 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 cells in 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 cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and 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 cells in B6.MRL Fas lpr/lpr mice.