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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3745-3749
IMMUNOBIOLOGY
The B-cell receptor of a hepatitis C virus (HCV)-associated
non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating
HCV in lymphomagenesis
Elizabeth R. Quinn,
Chunghuang Hubert Chan,
Kenneth
G. Hadlock,
Steven K. H. Foung,
Mike Flint, and
Shoshana Levy
From the Departments of Medicine/Division of Oncology
and Pathology, Stanford University Medical Center, Stanford, CA.
Hepatitis C virus (HCV) infection is associated with extrahepatic
B-cell lymphoproliferative disorders. To determine whether a viral
antigen drives this B-cell expansion, the B-cell receptors were cloned
from HCV-associated lymphomas and were expressed as soluble
immunoglobulins. The rescued immunoglobulins were then tested for their
ability to bind the HCV-E2 envelope glycoprotein, an antigen that was
previously implicated in the pathogenesis of HCV-associated B-cell
diseases. One of 2 lymphoma immunoglobulin test cases bound the E2
protein in a manner identical to a bona fide human anti-E2 antibody.
Moreover, it bound E2 from multiple viral genotypes, suggesting
reactivity with a conserved E2 epitope. These findings support the
hypothesis that some HCV-associated lymphomas originate from B cells
that were initially activated by the HCV-E2 protein and might explain
the association between HCV infection and some B-cell
lymphoproliferative disorders.
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