Abstract |
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.
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Authors | C H Chan, K G Hadlock, S K Foung, S Levy |
Journal | Blood
(Blood)
Vol. 97
Issue 4
Pg. 1023-6
(Feb 15 2001)
ISSN: 0006-4971 [Print] United States |
PMID | 11159532
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Hepatitis C Antibodies
- Immunoglobulin Heavy Chains
- Immunoglobulin Variable Region
- Viral Envelope Proteins
- glycoprotein E2, Hepatitis C virus
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Topics |
- Amino Acid Sequence
- Clonal Deletion
- DNA Mutational Analysis
- Genes, Immunoglobulin
- Hepacivirus
(immunology)
- Hepatitis C
(complications, immunology)
- Hepatitis C Antibodies
(immunology)
- Humans
- Hybridomas
(immunology)
- Immunoglobulin Heavy Chains
(genetics)
- Immunoglobulin Variable Region
(genetics)
- Lymphoma, B-Cell
(etiology, immunology)
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Alignment
- Sequence Homology, Amino Acid
- Viral Envelope Proteins
(immunology)
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