IgM plays an important role in induction of collagen-induced arthritis

Clin Exp Immunol. 2007 Sep;149(3):579-85. doi: 10.1111/j.1365-2249.2007.03440.x. Epub 2007 Jun 22.

Abstract

IgM is one major type of B cell receptor (BCR) expressed on most of the B cells from immature to mature stages. During normal B cell ontogeny, signals transduced through the IgM BCR play an important role in regulating B cell maturation and survival at multiple checkpoints. In addition, IgM BCR is also required for antigen-dependent differentiation and activation of B cells. However, whether IgM BCR-mediated signalling is important for the pathogenesis of autoimmune diseases remains elusive. Using IgM-deficient mice, we examined the effect of absence of IgM on the development of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA). Compared to their wild-type littermates, IgM-deficient mice were either resistant to arthritis induction or developed significantly less severe arthritis. There was a significant decrease of autoantibody production in IgM-deficient mice, particularly IgG2a antibodies, which is believed to be pathogenic in CIA. Thus, although IgM(-/-) mice have relatively normal B cell development with IgD BCR replacing IgM BCR, the absence of IgM-mediated signals has a profound impact on the development of CIA, indicating that IgM plays an important role in the development and pathogenesis of autoimmune arthritis and IgM-mediated signalling is critical in the generation of pathogenic autoreactive antibodies.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Autoantibodies / biosynthesis
  • Autoimmune Diseases / immunology
  • B-Lymphocyte Subsets / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / deficiency
  • Immunoglobulin M / immunology*
  • Immunoglobulin M / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred DBA
  • Rheumatoid Factor / biosynthesis
  • T-Lymphocytes / immunology

Substances

  • Autoantibodies
  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin M
  • Rheumatoid Factor