IgM plays an important role in induction of collagen-induced arthritis.
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.
Zheng
B
B
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Zhang
X
X
Guo
L
L
Han
S
S
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D012217:Rheumatoid Factor / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012217:Rheumatoid Factor