Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors

Franco Fais, Fabio Ghiotto, Shiori Hashimoto, Brian Sellars, Angelo Valetto, Steven L. Allen, Philip Schulman, Vincent P. Vinciguerra, Kanti Rai, Laura Z. Rassenti, Thomas J. Kipps, Guillaume Dighiero, Harry W. Schroeder, Manlio Ferrarini, Nicholas Chiorazzi

Research output: Contribution to journalArticlepeer-review

Abstract

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged V(H) genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain V(H), D, and J(H) genes among B-CLL cells. In addition, they indicate that the V. genes of ~50% of the IgM+ B-CLL cells and ~ 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the V(H) family expressed by the B-CLL cell (V(H)3 expressers displaying more mutation than V(H)1 and V(H)4 expressers). In addition, the extent of mutation can be sizeable with ~32% of the IgM+ cases and ~68% of the non- IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated V(H) genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and J(H) gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the V(H) genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the 'experienced' or 'memory' CD5+ B cell subset.

Original languageEnglish
Pages (from-to)1515-1525
Number of pages11
JournalJournal of Clinical Investigation
Volume102
Issue number8
Publication statusPublished - Oct 15 1998

Keywords

  • Antibodies
  • Antigens
  • Hematologic neoplasms
  • Mutational analysis, DNA
  • Receptors, antigen, B cell

ASJC Scopus subject areas

  • Medicine(all)

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