Immunoglobulin V gene expression in CD5 B-cell malignancies

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphomas (SLL) generally are malignancies of CD5 B cells. Immunophenotypic and clinicopathologic data, however, are required to distinguish subtypes that apparently have a different cytogenesis than that of conventional CLL or SLL. In addition to expressing CD5, neoplastic cells of the latter are also distinctive in that they frequently coexpress surface immunoglobulin (Ig), bearing one or more cross-reactive idiotypes (CRIs) (e.g. 17.109, G6,) that commonly are found on monoclonal IgM autoantibodies. The frequent occurrence of such CRIs reflects both the biased rearrangement and subsequent selected expression of Ig V genes with little or no somatic mutation. IgM/L CLL, for example, frequently (8/33) harbor abortive Ig rearrangements involving Humkv325, the VK gene encoding the 17.109-CRI. Also, the VH1 gene(s) encoding the G6 CRI accounts for over 10% of all VH genes and over 60% of all the VH1 genes used in randomly selected common CLL/SLL. Furthermore, comparison with the Ig expressed by nonmalignant G6 CRI+ B cells reveals an apparent restriction in the CDR3 of IgH expressed by G6 CRI+ CLL. Coupled with the observed potential bias in antibody light chain and heavy chain pairing in B-CLL, these data suggest that the autoantibodies expressed in this disease are selected based on antigen-binding activity. Collectively, our studies indicate that nonstochastic Ig V gene rearrangement and subsequent selection may influence the Ig repertoire expressed in this common B-cell malignancy.