Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia.
Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.
North Shore-LIJ Research Institute, 350 Community Dr., Manhasset, NY 11030, USA.
Bradley T
BT
Messmer
Emilia
E
Albesiano
Dimitar G
DG
Efremov
Fabio
F
Ghiotto
Steven L
SL
Allen
Jonathan
J
Kolitz
Robin
R
Foa
Rajendra N
RN
Damle
Franco
F
Fais
Davorka
D
Messmer
Kanti R
KR
Rai
Manlio
M
Ferrarini
Nicholas
N
Chiorazzi
D000595:Amino Acid Sequence; D016000:Cluster Analysis; D030541:Databases, Genetic; D014644:Genetic Variation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell