The role of clonal selection and somatic mutation in autoimmunity

Nature. 1987 Aug 27-Sep 2;328(6133):805-11. doi: 10.1038/328805a0.

Abstract

Polyclonal activation has been proposed as the reason that autoantibodies are produced during autoimmune disease. This model denies a role for specific antigen selection of B cells and predicts instead a multiclonal population of unmutated or randomly mutated autoantibodies. We have found that the genetic features and clonal composition of spontaneously derived immunoglobulin G (IgG) antiself-IgG (rheumatoid factor (RF] autoantibodies derived from the autoimmune MRL/lpr mouse strain are inconsistent with both the predictions of this model and the actual outcome of experimental polyclonal activation. Instead we have found that MRL/lpr RFs are oligoclonal or even monoclonal in origin. They harbour numerous somatic mutations which are distributed in a way that suggests immunoglobulin-receptor-dependent selection of these mutations. In this sense, the MRL/lpr RFs resemble antibodies elicited by exogenous antigens after secondary immunization. The parallels suggest that, like secondary immune responses, antigen stimulation is important in the generation of MRL/lpr RFs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantibodies / genetics*
  • Autoantigens / immunology
  • Autoimmune Diseases / genetics*
  • B-Lymphocytes / immunology
  • Base Sequence
  • Clone Cells / immunology
  • Hybridomas / immunology
  • Immunoglobulin G / genetics
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mutation*
  • Rheumatoid Factor / genetics

Substances

  • Autoantibodies
  • Autoantigens
  • Immunoglobulin G
  • Rheumatoid Factor