Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia

J Exp Med. 2004 Aug 16;200(4):519-25. doi: 10.1084/jem.20040544.

Abstract

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cluster Analysis
  • Databases, Genetic
  • Genetic Variation*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Light Chains / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Molecular Sequence Data
  • Mutation / genetics
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, B-Cell / immunology
  • Sequence Alignment
  • Sequence Analysis, DNA

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell