Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM

Individuals with systemic lupus erythematosus and rheumatoid arthritis are characterized by the presence of high levels of circulating IgM and IgG aut oantibodies. Although IgG autoantibodies often are pathogenic, the role of IgM autoantibodies in autoimmune disease is not clear. Using mice that are unable to secrete IgM but are able to express surface IgM and IgD and to se crete other classes of immunoglobulins, we examined the effect of the absen ce of secreted IgM in the development of IgG autoantibodies and autoimmune disease in lupus-prone lymphoproliferative (Ipr) mice. Compared with regula r Ipr mice, Ipr mice that lack secreted IgM developed elevated levels of Ig G autoantibodies to double-stranded DNA and histones and had more abundant deposits of immune complexes in the glomeruli; they also suffered more seve re glomerulonephritis and succumbed to the disease at an earlier age. Simil arly, the absence of secreted IgM also resulted in an accelerated developme nt of IgG autoantibodies in normal mice. These findings suggest that secret ed IgM, including IgM autoantibodies produced naturally or as part of an au toimmune response, may lessen the severity of autoimmune pathology associat ed with IgG autoantibodies.