Extensive and Selective Mutation of a Rearranged VH5 Gene in Human B Cell Chronic Lymphocytic Leukemia

Jilian Cai, Caroline Humphries, Andrea Richardson, Philip W. Tucker

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55 Scopus citations

Abstract

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 nudeotide 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 CD5H B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region I (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.

Original languageEnglish (US)
Pages (from-to)1073-1081
Number of pages9
JournalJournal of Experimental Medicine
Volume176
Issue number4
DOIs
StatePublished - Oct 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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