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

Bradley T. Messmer, Emilia Albesiano, Dimitar G. Efremov, Fabio Ghiotto, Steven L. Allen, Jonathan Kolitz, Kobin Foa, Rajendra N. Damle, Franco Fais, Davorka Messmer, Kanti R. Rai, Manlio Ferrarini, Nicholas Chiorazzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)519-525
Number of pages7
JournalJournal of Experimental Medicine
Volume200
Issue number4
DOIs
Publication statusPublished - Aug 16 2004

Keywords

  • Antibodies
  • Autoantibodies
  • B lymphocytes
  • Human
  • Ig variable region genes

ASJC Scopus subject areas

  • Immunology

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