Immunoglobulin isotype determines pathogenicity in antibody-mediated myocarditis in naive mice

Antimyosin reactivity is associated with cardiac damage in autoimmune myoca rditis, an inflammatory heart disease characterized by a cellular infiltrat e in the myocardium and myocyte necrosis, We are interested in the pathogen icity of antimyosin antibodies and their ability to cause autoimmune myocar ditis. We have shown that antimyosin antibodies of the IgG isotype will ind uce disease in the DBA/2 mouse. In the present study, we show that IgM anti myosin antibodies do not induce myocarditis; however, these same antibodies become pathogenic when converted to the IgC isotype. Although IgM antibodi es can penetrate the myocardium during cardiac inflammation, they are usual ly less able to leave the vascular compartment and penetrate cardiac tissue , thus accounting for their lack of pathogenicity. Thus, antimyosin B cells may be potentially pathogenic only after antigen activation and heavy chai n class switching or under conditions that alter vascular permeability in t he heart.