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.
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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.)
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Chemical References |
- Immunoglobulin G
- Receptors, Antigen, B-Cell
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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
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