Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections

Barbara Oliviero, Antonella Cerino, Stefania Varchetta, Enrica Paudice, Somnath Pai, Serena Ludovisi, Marco Zaramella, Giuseppe Michelone, Paolo Pugnale, Francesco Negro, Vincenzo Barnaba, Mario U. Mondelli

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: 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.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalJournal of Hepatology
Volume55
Issue number1
DOIs
Publication statusPublished - Jul 2011

Keywords

  • Activation markers
  • B cells
  • ELISpot
  • Flow cytometry
  • HBV
  • HCV

ASJC Scopus subject areas

  • Hepatology

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