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

Academic Article

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.
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    Digital Object Identifier (doi)

    Author List

  • Fais F; Ghiotto F; Hashimoto S; Sellars B; Valetto A; Allen SL; Schulman P; Vinciguerra VP; Rai K; Rassenti LZ
  • Start Page

  • 1515
  • End Page

  • 1525
  • Volume

  • 102
  • Issue

  • 8