Extensive and Selective Mutation of a Rearranged V_H5 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 V_H and V_L genes rearranged and/or expressed in CLL have few and apparently random mutations. However, in this study, we have found that the rearranged V_H251 gene, one of the three-membered V_H5 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 CD5_H 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.