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-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.
Ghiotto
Fabio
F
Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York, USA.
Fais
Franco
F
Valetto
Angelo
A
Albesiano
Emilia
E
Hashimoto
Shiori
S
Dono
Mariella
M
Ikematsu
Hideyuki
H
Allen
Steven L
SL
Kolitz
Jonathan
J
Rai
Kanti R
KR
Nardini
Marco
M
Tramontano
Anna
A
Ferrarini
Manlio
M
Chiorazzi
Nicholas
N
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
D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell