Elevated levels of IgG and IgM autoantibodies are often associated with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several lines of evidence suggest that increased levels of IgG are pathogenic, whereas an increased level of IgM is not. Previous studies have shown that mice deficient in secreted IgM (sIgM), or deficient in various components of the complement system, have an impaired IgG response to a T cell-dependent antigen. This indicates that sIgM and complement are involved in mediating the IgG antibody responses to foreign antigens. In order to elucidate the role of sIgM in the pathogenesis of autoimmune disease, a mutation was introduced into the lupus-prone lymphoproliferative (lpr) mouse, in which B cells are incapable of secreting IgM, while still capable of expressing surface IgM and IgD and secreting IgG antibodies. To investigate the role of secreted IgM autoantibodies in the pathogenesis of autoimmune disease.