Molecular analysis of VH and VL regions expressed in IgG-bearing chronic lymphocytic leukemia (CLL): further evidence that CLL is a heterogeneous group of tumors.

We report the heavy (H) and light (L) chain variable (V) region sequences of cDNAs encoding the Ig receptor of two cases of CD5+ IgG-bearing CLL P87 and P103. In both CLL cases the H chain was encoded by members of the VH3 gene family. The L chain expressed by P87 belonged to the V lambda IV subgroup, whereas P103 used a member of the V kappa III subgroup. The VH3.P87 gene differed by only three nucleotides from 38P1, a VH3 gene previously cloned from a fetal liver cDNA library. Nucleotide sequence analysis demonstrated that the V kappa III.P103 gene differed by seven nucleotides from its most homologous germline counterpart, the Humkv325 gene, a highly conserved gene frequently expressed in IgM-bearing CLL. The nucleotide sequences of VH3.P103 and V lambda IV.P87 could not be reliably matched with reported germline V genes. The analysis of multiple independently obtained VH and VL cDNA clones from each tumor showed a lack of intraclonal diversification. The data show that V regions expressed in isotype-switched CD5+ CLL may be either in/near germline configuration or somatically mutated. Furthermore, these tumors, like their IgM-bearing counterparts, do not seem to undergo intraclonal diversification.