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

Abstract

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.

• Authors: Fabio Ghiotto, Franco Fais, Angelo Valetto, Emilia Albesiano, Shiori Hashimoto, Mariella Dono, Hideyuki Ikematsu, Steven L Allen, Jonathan Kolitz, Kanti R Rai, Marco Nardini, Anna Tramontano, Manlio Ferrarini, Nicholas Chiorazzi
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 113 Issue 7 Pg. 1008-16 (Apr 2004) ISSN: 0021-9738 [Print] United States
• PMID: 15057307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Immunoglobulin G
• Receptors, Antigen, B-Cell

Topics

• B-Lymphocytes (immunology, metabolism)
• Humans
• Immunoglobulin G (genetics, immunology)
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, metabolism)
• Models, Molecular
• Protein Structure, Tertiary
• Receptors, Antigen, B-Cell (metabolism)
• Sequence Analysis, Protein