A transgenic model of autoimmune hemolytic anemia

J Exp Med. 1992 Jan 1;175(1):71-9. doi: 10.1084/jem.175.1.71.

Abstract

We made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the single-chain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to self-antigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.

MeSH terms

  • Anemia, Hemolytic / genetics*
  • Anemia, Hemolytic / immunology
  • Animals
  • Antibodies, Monoclonal
  • Antibody Formation
  • Autoantibodies / genetics*
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • B-Lymphocytes / immunology*
  • Bone Marrow / immunology
  • Crosses, Genetic
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / immunology
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Genes, Immunoglobulin*
  • Immunoglobulin G / analysis
  • Immunoglobulin G / genetics
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Light Chains / genetics*
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spleen / immunology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains