Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients

Cell Mol Immunol. 2015 May;12(3):309-16. doi: 10.1038/cmi.2015.25. Epub 2015 Apr 6.

Abstract

B cells play an important role in the clearance of hepatitis B virus (HBV) and protection against reinfection. However, the functional characteristics of these cells that are associated with the outcome of chronic HBV infection remain unknown. We comprehensively investigated the frequency, phenotype, and function of peripheral B-cell subsets from CHB patients in different phases: immune tolerance (IT), immune activation (IA), immune clearance (IC), responders with HBsAg seroconversion (resolved patients, RP), and healthy controls (HC). IA patients displayed lower percentages of peripheral blood memory B cells compared with the other groups. Overall polyclonal activation of B cells, indicated by higher levels of activation markers and secretion of IgG and IgM, was observed in IA patients. This B-cell hyperactivation could be induced by increased IFN-α and soluble CD40 ligands in IA patients. Notably, the expression of the co-stimulator molecule CD80 and serum HBsAb and the frequency of HBsAg-specific B cells were significantly decreased in IT, IA, and IC patients compared with HC subjects. More importantly, the B-cell hyperactivation, co-stimulatory molecule downregulation and HBsAg-specific B-cell impairment were reversed in RP patients. The reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Antigens, Viral / immunology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • B7-1 Antigen / metabolism
  • CD40 Antigens / metabolism
  • Disease Progression
  • Female
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Immune Tolerance
  • Immunologic Memory
  • Immunophenotyping
  • Interferon-alpha / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Seroconversion*
  • Viral Load
  • Young Adult

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • B7-1 Antigen
  • CD40 Antigens
  • Interferon-alpha