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Blood, 15 February 2001, Vol. 97, No. 4, pp. 1023-1026
IMMUNOBIOLOGY
VH1-69 gene is preferentially used by
hepatitis C virus-associated B cell lymphomas and by normal B cells
responding to the E2 viral antigen
Chunghuang Hubert Chan,
Kenneth G. Hadlock,
Steven K. H. Foung, and
Shoshana Levy
From the Department of Medicine, Division of Oncology
and Pathology, Stanford University Medical Center, Stanford, CA.
Hepatitis C virus (HCV)-associated B cell lymphomas were
previously shown to express a restricted repertoire of immunoglobulin VH and VL genes, VH1-69 and
V A27, respectively. Although this suggests a role for antigen
selection in the pathogenesis of these lymphomas, the driving antigen
involved in the clonal expansion has not been identified. B cell
response to a viral antigen, the HCV envelope glycoprotein 2 (E2), was
analyzed in an asymptomatic HCV-infected patient. Single B cells,
immortalized as hybridomas and selected for binding E2, were analyzed
for their V gene usage. Sequences of these V region genes demonstrated
that each hybridoma expressed unique VH and VL
genes. Remarkably, these anti-E2 hybridomas preferentially used the
VH1-69 gene. Analysis of replacement to silent mutation
ratios indicated that the genes underwent somatic mutation and
antigenic selection. In a separate report, human anti-E2 antibodies
were also shown to express the same VH gene. These data
strengthen the hypothesis that the HCV-associated lymphomas are derived
from clonally expanded B cells stimulated by HCV.
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