Analysis of VH251 gene mutation in chronic lymphocytic leukemia (CLL) and normal B-cell subsets.
B-cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have low and random mutations. In this study, however, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03%, and there is a high ratio of replacement to silent mutation in CDRs relative to FWRs. CDR1 mutation is particularly prevalent, and interchanges often lead to acquisition of charge. In VH251 rearranged in CD5+ and CD5- cord-blood B cells, adult peripheral-blood B cells and EBV-transformed CD5+ B-cell lines, the somatic mutation levels are much lower (0.45%, 0.93%, and 1.92%, respectively) with concomitantly lower replacement to silent ratios in CDRs relative to FWRs. The extensive and highly selective somatic mutation of VH251 used in CD5+ CLL cells strongly suggests that part of CLL is generated under the influence of antigen selection and stimulation.
Cai
J
J
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Humphries
C
C
Lutz
C
C
Tucker
P W
PW
D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D004247:DNA