B lymphocytes may escape tolerance by revising their antigen receptors

J Exp Med. 1993 Apr 1;177(4):1165-73. doi: 10.1084/jem.177.4.1165.

Abstract

To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double-stranded DNA (dsDNA) and their L chain sequences showed a biased use of V kappa and J kappa gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V kappa group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V kappa genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V kappa genes. The most frequently observed gene, a member of the V kappa 12/13 group, was identified in 16 hybrids. In addition, the majority of V kappa genes used J kappa 5. We interpret the skewed representation of V kappa and J kappa gene segments to result from negative selection. Based on the data, we suggest that V kappa rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self-reactive Ig.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Blotting, Southern
  • DNA
  • Female
  • Gene Rearrangement, B-Lymphocyte
  • Hybridomas
  • Immune Tolerance*
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Variable Region / genetics
  • Male
  • Mice
  • Molecular Sequence Data
  • Receptors, Antigen, B-Cell / immunology*

Substances

  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell
  • DNA