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

Blood. 2001 Dec 15;98(13):3745-9. doi: 10.1182/blood.v98.13.3745.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • B-Lymphocytes / immunology
  • Cloning, Molecular
  • Epitopes / metabolism
  • Gene Expression
  • Genotype
  • 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
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / virology*
  • 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*

Substances

  • Epitopes
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Receptors, Antigen, B-Cell
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus

Associated data

  • GENBANK/AF372842
  • GENBANK/AF372843
  • GENBANK/AF372844
  • GENBANK/AF372845