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.

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.

• 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.)

Chemical References

• Hepatitis C Antibodies
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Viral Envelope Proteins
• glycoprotein E2, Hepatitis C virus

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)