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

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 V H DJ H and V L J L genes of 25 non–IgM...

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Veröffentlicht in:The Journal of clinical investigation 2004-04, Vol.113 (7), p.1008-1016
Hauptverfasser: Ghiotto, Fabio, Fais, Franco, Valetto, Angelo, Albesiano, Emilia, Hashimoto, Shiori, Dono, Mariella, Ikematsu, Hideyuki, Allen, Steven L., Kolitz, Jonathan, Rai, Kanti R., Nardini, Marco, Tramontano, Anna, Ferrarini, Manlio, Chiorazzi, Nicholas
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Sprache:eng
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Zusammenfassung: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 V H DJ H and V L J L 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.
ISSN:0021-9738
DOI:10.1172/JCI200419399