title: Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections.
abstract: OBJECTIVE
  Chronic microbial infections are frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection.
  
  
  METHODS
  We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls. B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand±IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide±IL-2, as innate immunity signal. Proliferation was examined by flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG.
  
  
  RESULTS
  A significantly higher proportion of B cells from both HCV- and HBV-infected patients expressed activation markers compared with controls and a positive correlation was found between CXCR3(+) B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infected patients. Moreover, patients' activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustion marker.
  
  
  CONCLUSIONS
  B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation.
authors.affiliation: Department of Infectious Diseases, University of Pavia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Oliviero
authors.forename: Antonella
authors.initials: A
authors.lastname: Cerino
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
authors.forename: Enrica
authors.initials: E
authors.lastname: Paudice
authors.forename: Somnath
authors.initials: S
authors.lastname: Pai
authors.forename: Serena
authors.initials: S
authors.lastname: Ludovisi
authors.forename: Marco
authors.initials: M
authors.lastname: Zaramella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Michelone
authors.forename: Paolo
authors.initials: P
authors.lastname: Pugnale
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D055815:Young Adult
chemical_list: D012367:RNA, Viral