In vitro synthesis and immunoregulation of antibody to hepatitis B surface antigen in man

Peripheral blood mononuclear cells (PBMC) from 16 chronic hepatitis B surface antigen (HBsAg) carriers and from 10 immune individuals (anti-HBs and/or anti-HBc core antigen positive) were studied for their ability to synthesize antibody to hepatitis B viral antigens in vitro. Pokeweed mitogen (PWM)-stimulated B lymphocytes from carriers, synthesized polyclonal IgG and IgM normally but did not synthesize detectable antibody to HBsAg (anti-HBs) even in the presence of T lymphocyte help and the absence of T lymphocyte suppression from immune individuals. In contrast, B lymphocytes from 80% of immune individuals synthesized anti-HBs in vitro. In cell-mixing experiments, T lymphocytes from carriers were found to provide normal helper function for immunoglobulin and anti-HBs production by B lymphocytes from immune individuals. In addition, the degree of suppressor T lymphocyte activity of chronic carriers was not sufficient to explain the lack of anti-HBs production. The effect of purified HBsAg on anti-HBs synthesis by PBMC from immune individuals was determined. Incubating PBMC for periods ranging from 10 min to 10 days in the presence of concentrations of HBsAg varying from 10 pg/ml to 10 μg/ml had no effect on the synthesis of anti-HBs by PBMC. These results suggest that chronic HBsAg carriers lack circulating B lymphocytes capable of producing anti-HBs and that this cannot be explained by the presence of large amounts of circulating HBsAg.