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

• Published in: Blood 2001-12, Vol.98 (13), p.3745-3749
• Main Authors: Quinn, Elizabeth R., Chan, Chunghuang Hubert, Hadlock, Kenneth G., Foung, Steven K.H., Flint, Mike, Levy, Shoshana
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; B-Lymphocytes - immunology; Biological and medical sciences; Cloning, Molecular; Epitopes - metabolism; Gene Expression; Genotype; Hematologic and hematopoietic diseases; Hepacivirus - immunology; Hepatitis C; Humans; Immunoglobulin Heavy Chains - chemistry; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Light Chains - chemistry; Immunoglobulin Light Chains - genetics; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Immunoglobulins - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - immunology; Lymphoma, Non-Hodgkin - virology; Medical sciences; Molecular Sequence Data; Mutation; Protein Conformation; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.13.3745

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.