Autoimmune myocarditis does not require B cells for antigen presentation

T cells constitute the pathogenic effector cell population in autoimmune my ocarditis in BALB/c mice, Using mice rendered deficient for B cells by a ta rgeted disruption to the IgM transmembrane domain or by treatment with anti -IgM Ab from birth, we asked whether B cells are a critical APC in the indu ction of autoimmune myocarditis. B cell-deficient mice immunized with cardi ac myosin develop myocarditis comparable in incidence and severity to that in wild-type mice, suggesting that autoreactive T cells that cause myocardi tis in BALB/c mice are activated by macrophages or dendritic cells. Since i t does not appear that presentation of cryptic epitopes is critical for the breakdown of self tolerance, potentially pathogenic T cells recognizing do minant myosin epitopes must have escaped tolerization. Either anatomic sequ estration of cardiac myosin peptide-MHC complexes or subthreshold presentat ion of cardiac myosin peptides by conventional APC can explain the survival of these autoreactive T cells.