V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen.
Hepatitis C virus (HCV)-associated B cell lymphomas were previously shown to express a restricted repertoire of immunoglobulin V(H) and V(L) genes, V(H)1-69 and VkappaA27, 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 V(H) and V(L) genes. Remarkably, these anti-E2 hybridomas preferentially used the V(H)1-69 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 V(H) gene. These data strengthen the hypothesis that the HCV-associated lymphomas are derived from clonally expanded B cells stimulated by HCV.
Chan
C H
CH
Department of Medicine, Division of Oncology and Pathology, Stanford University Medical Center, Stanford, CA, USA.
Hadlock
K G
KG
Foung
S K
SK
Levy
S
S
D000595:Amino Acid Sequence; D017637:Clonal Deletion; D004252:DNA Mutational Analysis; D005803:Genes, Immunoglobulin; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000276:immunology*
D018937:Hepatitis C Antibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus