Somatic hypermutation, clonal diversity, and preferential expression of the V(H) 51p1/V(L) kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas

Martin Ivanovski, Federico Silvestri, Gabriele Pozzato, Shubha Anand, Cesare Mazzaro, Oscar R. Burrone, Dimitar G. Efremov

Research output: Contribution to journalArticle

Abstract

A high prevalence of chronic hepatitis C virus (HCV) infection has recently been shown in a subset of B-cell non-Hodgkin's lymphomas, most of which belong to the lymphoplasmacytoid lymphoma/immunocytoma subtype and are characterized by the production of a monoclonal IgM cryoglobulin with rheumatoid factor activity. To better define the stage of differentiation of the malignant B call and to investigate the role of chronic antigen stimulation in the pathogenesis of the HCV-associated immunocytomas, 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 51p1 V(H) gene in combination with the kv325 V(L) gene. Moreover, a monoclonal 51p1-expressing B-cell population was detected in 4 of the remaining immunocytomas by an allele-specific Ig gene fingerprinting assay, indicating that HCV-associated immunocytomas represent clonal proliferations of a highly selected B-cell population. Somatic mutations and intraclonal diversity were observed in all of the lymphoma V genes, and clonally related IgM and IgG V. transcripts indicative of isotype switching were present in one case. These findings are consistent with an antigen-driven process and support a role for chronic antigen stimulation in the growth and clonal evolution of HCV-associated immunocytomas.

Original languageEnglish
Pages (from-to)2433-2442
Number of pages10
JournalBlood
Volume91
Issue number7
Publication statusPublished - Apr 1 1998

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ASJC Scopus subject areas

  • Hematology

Cite this

Ivanovski, M., Silvestri, F., Pozzato, G., Anand, S., Mazzaro, C., Burrone, O. R., & Efremov, D. G. (1998). Somatic hypermutation, clonal diversity, and preferential expression of the V(H) 51p1/V(L) kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas. Blood, 91(7), 2433-2442.