Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune 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.

Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions

“…In this current study, many plasma cells containing Russell bodies (called mott cells) and the accumulation of immunoglobulin G-positive cells were observed at the peribronchial lesions of 0.4 and 3.0 mg treated mice at 4 months after instillation. In general, mott cells are regarded as plasma cells undergoing excessive synthesis of immunoglobulin and defective in secretion [31] www.fhc.viamedica.pl cells are rare in normal tissue but frequently encountered in lymphoid tissues of murine and human autoimmune diseases [58] and in chronic inflammatory lesions with hyper-activation of the immune system by pathogens [59]. Thus, the presence of plasma cells containing Russell bodies observed in the ASD treated mice in this study suggests that the activation of antibody-mediated immunity occurred in addition to cell-mediated immunity, which could be in a state of hyper-immunization.…”

FcμR Interacts and Cooperates with the B Cell Receptor To Promote B Cell Survival

“…FcmR-deficient mice produce elevated IgG autoantibodies as they age (19)(20)(21)(22), suggesting that FcmR is required for maintaining selftolerance. The results of the current study demonstrate that FcmR promotes BCR-triggered survival of mature B cells.…”

“…The recently identified IgM FcR (FcmR) (17,18) has been shown to play a critical role in IgM homeostasis, B cell development and survival, germinal center formation, and humoral immune responses as well as in prevention of autoantibody production (19)(20)(21)(22). It remains unclear, however, how FcmR regulates B cell development and function.…”

Nomenclature of Toso, Fas Apoptosis Inhibitory Molecule 3, and IgM FcR

“…The Journal of Immunology, 2015, 194: 4055-4057. Two laboratories (Ohno and Mak) had generated Fcmr/ Toso-deficient mice, and from 2012 to 2015 four groups of investigators independently characterized their phenotypes (11)(12)(13)(14)(15)(16)(17)(18)(19). Clear differences in the reported phenotypes, in addition to the cellular distribution of FcmR/Toso, were evident but are not discussed in this article because they are not directly related to the topic of this meeting.…”