Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.
B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mice genetically deficient in B cells (NOD.Kmu(null)) or rendered B cell-deficient by treatment from birth with anti-IgM develop minimal SAT. B cells were required some time in the first 4-6 wk after birth, because NOD.Kmu(null) or NOD.H-2h4 mice did not develop SAT when they were reconstituted with B cells as adults. The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cells as adults produced autoantibodies but did not develop SAT. B cell-deficient mice developed SAT if their T cells developed from bone marrow precursors in the presence of B cells. Because B cells are required early in life and their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4-6 wk after birth.
Braley-Mullen
H
H
Departments of Internal Medicine and Medical Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA. mullenh@health.missouri.edu
Yu
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007075:Immunoglobulin M; C044203:anti-IgM; C006606:anti-thyroglobulin; D013954:Thyroglobulin