Mechanisms of autoantibody diversification to SLE-related autoantigens

Ann N Y Acad Sci. 2003 Apr;987:91-8. doi: 10.1111/j.1749-6632.2003.tb06036.x.

Abstract

Systemic lupus erythematosus is a prototype of systemic autoimmunity with autoantibodies (autoAbs) to ribonucleoproteins such as Ro/La, snRNP, dsDNA, and other cellular constituents. A/J mice were used to explore the mechanism of autoAb diversification with recombinant proteins and synthetic peptides. Previous studies showed that Ro60(316-335) induced Abs to Ro60, La, and snRNP proteins. Specific Abs to determinants outside Ro60(316-335) were detected. Absorption experiments showed that Abs to La and snRNP proteins were due to the induction of anti-Ro60 Abs cross-reactive with these peptides. With snRNP proteins, SmD, SmB, and A-RNP as immunogens, specific patterns of intermolecular spreading were obtained in addition to Abs to the immunogens. With SmD-immunized mice, specific Abs to A-RNP and SmB were detected. With SmB as the immunogen, specific Abs to A-RNP were detected in the majority of the mice. Only in a rare incident, specific Abs to SmD were induced. In A-RNP-immunized mice, only Abs to the 70-kD U1-RNP were seen. In all cases, Abs capable of precipitating snRNP particles were detected. Thus, the intermolecular epitope spreading is immunogen-dependent. Evidence for the presence of cross-reactive T cells to more than one autoAg was obtained. The Ag-dependent unique patterns of Ab diversification will facilitate analyses of patients' sera. These results have implications regarding the nature of the Ag-driven autoimmune process.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Epitopes / immunology
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Mice
  • Molecular Sequence Data
  • Ribonucleoproteins, Small Nuclear / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Ribonucleoproteins, Small Nuclear