Autoimmune myocarditis does not require B cells for antigen presentation.
T cells constitute the pathogenic effector cell population in autoimmune myocarditis in BALB/c mice. Using mice rendered deficient for B cells by a targeted 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 induction of autoimmune myocarditis. B cell-deficient mice immunized with cardiac myosin develop myocarditis comparable in incidence and severity to that in wild-type mice, suggesting that autoreactive T cells that cause myocarditis in BALB/c mice are activated by macrophages or dendritic cells. Since it does not appear that presentation of cryptic epitopes is critical for the breakdown of self tolerance, potentially pathogenic T cells recognizing dominant myosin epitopes must have escaped tolerization. Either anatomic sequestration of cardiac myosin peptide-MHC complexes or subthreshold presentation of cardiac myosin peptides by conventional APC can explain the survival of these autoreactive T cells.
Malkiel
S
S
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Factor
S
S
Diamond
B
B
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009218:Myosins / Q000008:administration & dosage / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; C044203:anti-IgM; D009218:Myosins