Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice

Nature. 1991 Jan 24;349(6307):331-4. doi: 10.1038/349331a0.

Abstract

Self-reactive B cells can be regulated by either deletion or inactivation. These manifestations of self-tolerance have been dramatically shown in transgenic mice in which the number of self-reactive cells has been artificially expanded. We have now extended these models to ask if B-cell tolerance as described for non-disease-associated antigens also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA antibodies are diagnostic of certain autoimmune syndromes in humans and are a characteristic of the murine model of systemic autoimmunity, the MRl/lpr mouse. Antibodies to both single-stranded and double-stranded DNA have been implicated in disease. By generating anti-DNA transgenic mice, we have addressed the question of whether DNA-specific B cells are regulated in normal (non-autoimmune) mice. We indeed found that most transgenic B cells bind DNA, yet we failed to detect secreted anti-DNA. We suggest that as a consequence of their self-reactivity these B cells are developmentally arrested.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Antinuclear / genetics*
  • Antibodies, Antinuclear / immunology
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Autoantigens / immunology
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology*
  • Base Sequence
  • DNA / immunology
  • DNA, Single-Stranded / immunology
  • Gene Expression Regulation*
  • Hybridomas / immunology
  • Immune Tolerance
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Transfection

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Autoantigens
  • DNA, Single-Stranded
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • DNA