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

J Clin Invest. 1998 Oct 15;102(8):1515-25. doi: 10.1172/JCI3009.


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 VH 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 VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH 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 VH 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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / immunology*
  • Binding Sites / genetics
  • CD5 Antigens
  • DNA, Complementary / genetics
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Humans
  • Immunoglobulin M / biosynthesis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Molecular Sequence Data
  • Mutation*
  • Reading Frames
  • Receptors, Antigen, B-Cell / genetics*
  • Sequence Analysis, DNA


  • CD5 Antigens
  • DNA, Complementary
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell