Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia.
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 few and apparently random mutations. However, in this study, 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% in B-CLLs whereas the somatic mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in CLLs is particularly prevalent, and interchanges in CDRs often lead to acquisition of charge. Analysis of somatic mutations and mutations to charged residues demonstrated that the mutations in CLLs are highly selected.
Cai
J
J
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Humphries
C
C
Richardson
A
A
Tucker
P W
PW
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009838:Oligodeoxyribonucleotides; D012334:RNA, Neoplasm