Premium
Analysis of V H 251 Gene Mutation in Chronic Lymphocytic Leukemia (CLL) and Normal B‐Cell Subsets a
Author(s) -
CAI JILIAN,
HUMPHRIES CAROLINE,
LUTZ CHARLES,
TUCKER PHILIP W.
Publication year - 1992
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1992.tb24639.x
Subject(s) - cd5 , chronic lymphocytic leukemia , mutation , somatic cell , germline mutation , microbiology and biotechnology , biology , b cell , leukemia , gene , antigen , cancer research , genetics , antibody
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.