Kinetics of hepatitis B surface antigen-specific immune responses in acute and chronic hepatitis B or after HBs vaccination: stimulation of the in vitro antibody response by interferon gamma

Hepatology. 1999 Jan;29(1):238-44. doi: 10.1002/hep.510290120.


Because cellular and humoral immune responses against the hepatitis B virus (HBV) surface antigen (HBs) might be crucial to overcome HBV infection, HBs-specific B- and T-cell responses of HBV patients and HBs vaccine recipients were analyzed quantitatively and functionally. In patients with acute hepatitis B (AHB), transient high anti-HBs-secreting B-cell frequencies were observed early after clinical onset, whereas 1 patient who probably developed chronic infection and chronic HBV carriers had absent or weak B- and T-cell responses. In HBs vaccine recipients, maximal HBs-specific B- and T-cell responses were detected after the first injection that decreased gradually before anti-HBs antibodies appeared in serum. Years after vaccination, anti-HBs-secreting B cells were enriched in the bone marrow. After in vitro stimulation with HBsAg, peripheral blood mononuclear cells (PBMC) of only 1 of 5 acute and 1 of 6 chronic HBV patients, but of all 6 vaccine recipients, secreted varying amounts of interferon gamma (IFN-gamma), but no interleukin-4 (IL-4) or IL-5. Furthermore, the addition of IFN-gamma, but not of IL-2, -4, -12, or IFN-alpha, resulted in strong increases of anti-HBs-secreting B cells in vaccine recipients and chronic carriers. In conclusion, circulating anti-HBs-secreting B cells were significantly higher in early acute hepatitis B or early after HBs vaccination than in chronic hepatitis B and decreased in the follow-up as a result of compartmentalization to lymphoid tissues. Release of IFN-gamma by antigen-stimulated T cells might be critical for anti-HBs formation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / immunology
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • DNA, Viral / biosynthesis
  • Hepatitis B / immunology*
  • Hepatitis B Antibodies / biosynthesis*
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Interferon-gamma / pharmacology*
  • Kinetics
  • Recombinant Proteins
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccination


  • Cytokines
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Recombinant Proteins
  • Interferon-gamma