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

Int Immunol. 2014 Dec;26(12):659-72. doi: 10.1093/intimm/dxu070. Epub 2014 Jul 3.

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.

Keywords: FcμR; IgM; Mott cells; auto-antibody; marginal zone B cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoimmunity / genetics*
  • Autoimmunity / immunology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Lymphocyte Count
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Nephritis / genetics
  • Nephritis / immunology
  • Nephritis / mortality
  • Nephritis / pathology
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism*
  • Plasma Cells / pathology
  • Receptors, Fc / deficiency*
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism
  • Ribonucleoproteins, Small Nuclear / immunology

Substances

  • Autoantibodies
  • Receptors, Fc
  • Ribonucleoproteins, Small Nuclear
  • immunoglobulin M receptor