Treatment with high doses of anti-IgM prevents, but with lower doses accelerates autoimmune disease in (NZW x BXSB)F1 hybrid mice

J Immunol. 1987 Jun 15;138(12):4222-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / administration & dosage
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • B-Lymphocytes / immunology
  • Female
  • Hybridization, Genetic
  • Immunoglobulin M / administration & dosage
  • Immunoglobulin M / therapeutic use*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy*
  • Male
  • Mice
  • Mice, Inbred Strains / genetics
  • Mice, Inbred Strains / immunology
  • Mice, Mutant Strains / genetics
  • Mice, Mutant Strains / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Immunoglobulin M
  • anti-IgM