Treatment with high doses of anti-IgM prevents, but with lower doses accelerates autoimmune disease in (NZW x BXSB)F1 hybrid mice.
We have treated autoimmune-prone (NZW x BXSB)F1 hybrid mice with polyclonal rabbit anti-mouse IgM antibodies starting from birth to define conditions leading to quantitative and functional elimination of the B cell compartment and to determine the effect of anti-IgM treatment on the development of autoimmune disease. A maintenance dose of anti-IgM antibodies (600 micrograms/wk), which efficiently induced B cell depletion in various non-autoimmune strains of mice, was not sufficient to deplete B cells from autoimmune-prone (NZW x BXSB)F1 mice. (NZW x BXSB)F1 mice required approximately twice as many anti-IgM antibodies (1200 micrograms/wk) to maintain the suppression of B cell development. Continuous treatment with the sub-suppressive dose of anti-IgM antibodies led to a marked acceleration of autoimmune disease in (NZW x BXSB)F1 mice. In contrast, elimination of B cells in (NZW x BXSB)F1 mice with a higher dose of anti-IgM antibodies (1200 micrograms/wk) completely prevented autoantibody production, immune complex formation, and development of glomerulonephritis and vascular lesions associated with mononuclear cell infiltrations. Our results are a direct demonstration of the primary role of autoantibodies for the development of various tissue lesions seen in systemic lupus erythematosus (SLE) and indicates that autoreactive effector T cells, if they exist, play no major direct role in the pathogenesis of SLE, at least in (NZW x BXSB)F1 hybrid mice.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006824:Hybridization, Genetic; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; C044203:anti-IgM