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

Summary 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.