The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis

Hepatitis C virus (HCV) infection Is associated with extrahepatic B-cell ly mphoproliferative disorders. To determine whether a viral antigen drives th is B-cell expansion, the B-cell receptors were cloned from HCV-associated l ymphomas and were expressed as soluble immunoglobulins. The rescued immunog lobulins were then tested for their ability to bind the HCV-E2 envelope gly coprotein, an antigen that was previously implicated in the pathogenesis of HCV-associated B-cell diseases. One of 2 lymphoma immunoglobulin test case s bound the E2 protein in a manner identical to a bona fide human anti-E2 a ntibody. Moreover, it bound E2 from multiple viral genotypes, suggesting re activity with a conserved E2 epitope. These findings support the hypothesis that some HCV-associated lymphomas originate from B cells that were initia lly activated by the HCV-E2 protein and might explain the association betwe en HCV infection and some B-cell lymphoproliferative disorders. (C) 2001 by The American Society of Hematology.