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

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Abstract
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–γ), but no interleukin–4 (IL–4) or IL–5. Furthermore, the addition of IFN–γ, but not of IL–2, –4, –12, or IFN–α, 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–γ by antigen–stimulated T cells might be critical for anti–HBs formation.
Funding Information
  • Deutsche Forschungsgemeinschaft projects (SFB 311, A14, and Lo 621/1-1)