[HTML][HTML] Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

F Ghiotto, F Fais, A Valetto, E Albesiano… - The Journal of …, 2004 - Am Soc Clin Investig
F Ghiotto, F Fais, A Valetto, E Albesiano, S Hashimoto, M Dono, H Ikematsu, SL Allen…
The Journal of clinical investigation, 2004Am Soc Clin Investig
Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients
with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some
level of BCR structural restriction become transformed. While analyzing rearranged VHDJH
and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that
display strikingly similar BCRs (use of the same H-and L-chain V gene segments with
unique, shared heavy chain third complementarity-determining region [HCDR3] and light …
Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged VHDJH and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb’s reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG+ B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both.
The Journal of Clinical Investigation