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 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.
Quinn
E R
ER
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305-5151, USA.
Chan
C H
CH
Hadlock
K G
KG
Foung
S K
SK
Flint
M
M
Levy
S
S
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D000939:Epitopes / Q000378:metabolism; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007136:Immunoglobulins / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus