SOMATIC HYPERMUTATION, CLONAL DIVERSITY, AND PREFERENTIAL EXPRESSION OF THE V-H 51P1 V-L KV325 IMMUNOGLOBULIN GENE COMBINATION IN HEPATITIS-C VIRUS-ASSOCIATED IMMUNOCYTOMAS

A high prevalence of chronic hepatitis C virus (HCV) infection has rec ently been shown in a subset of B-cell non-Hodgkin's lymphomas, most o f which belong to the lymphoplasmacytoid lymphoma/immunocytoma subtype and are characterized by the production of a monoclonal IgM cryoglobu lin with rheumatoid factor activity. To better define the stage of dif ferentiation of the malignant B cell and to investigate the role of ch ronic antigen stimulation in the pathogenesis of the HCV-associated im munocytomas, we analyzed the variable (V) region gene repertoire in 16 cases with this type of tumor. The lymphoma-derived V gene sequences were successfully determined in 8 cases; 5 of them expressed the 5191 V-H gene in combination with the kv325 V-L gene. Moreover, a monoclona l 51p1-expressing B-cell population was detected in 4 of the remaining immunocytomas by an allele-specific Ig gene fingerprinting assay, ind icating that HCV-associated immunocytomas represent clonal proliferati ons of a highly selected B-cell population. Somatic mutations and intr aclonal diversity were observed in all of the lymphoma V genes, and cl onally related IgM and IgG V-H transcripts indicative of isotype switc hing were present in one case. These findings are consistent with an a ntigen-driven process and support a role for chronic antigen stimulati on in the growth and clonal evolution of HCV-associated immunocytomas. (C) 1998 by The American Society of Hematology.