title: 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.affiliation: Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ghiotto
authors.forename: Franco
authors.initials: F
authors.lastname: Fais
authors.forename: Angelo
authors.initials: A
authors.lastname: Valetto
authors.forename: Emilia
authors.initials: E
authors.lastname: Albesiano
authors.forename: Shiori
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Mariella
authors.initials: M
authors.lastname: Dono
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kolitz
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.forename: Marco
authors.initials: M
authors.lastname: Nardini
authors.forename: Anna
authors.initials: A
authors.lastname: Tramontano
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D020539:Sequence Analysis, Protein
chemical_list: D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell