title: Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.
abstract: OBJECTIVE
  Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma.
  
  
  METHODS
  Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage.
  
  
  CONCLUSIONS
  HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.
authors.affiliation: Department of Immunology, IRIS, Chiron S.r.l., Via Fiorentina, 1, 1-53100 Siena, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Galli-Stampino
authors.forename: A
authors.initials: A
authors.lastname: Pasqualini
authors.forename: G
authors.initials: G
authors.lastname: Pozzato
authors.forename: F
authors.initials: F
authors.lastname: Bonino
authors.forename: F
authors.initials: F
authors.lastname: Filipponi
authors.forename: M
authors.initials: M
authors.lastname: Mosca
authors.forename: F
authors.initials: F
authors.lastname: Masciopinto
authors.forename: S
authors.initials: S
authors.lastname: Abrignani
authors.forename: Y
authors.initials: Y
authors.lastname: Uematsu
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D016022:Case-Control Studies; D002999:Clone Cells / Q000276:immunology; D017931:DNA Primers; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains