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Somatic Hypermutation, Clonal Diversity, and Preferential Expression
of the VH 51p1/VL kv325 Immunoglobulin Gene
Combination in Hepatitis C Virus-Associated Immunocytomas
Martin Ivanovski,
Federico Silvestri,
Gabriele Pozzato,
Shubha Anand,
Cesare Mazzaro,
Oscar R. Burrone, and
Dimitar G. Efremov
From the Molecular Immunology Group, International Centre for Genetic
Engineering & Biotechnology; the Institute of Internal Medicine,
Ospedale di Cattinara, Trieste; and the 2nd Division of General
Medicine, Ospedale di Pordenone, Pordenone, Italy.
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 cell 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 VH gene in combination with the kv325
VL 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 VH 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.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2433-2442
© 1998 by The American Society of Hematology.
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