Antigen-induced in vitro antibody production in humans: a model for B cell activation and immunoregulation.

The precise events associated with B cell activation in humans are a subject of intense investigation. It has been difficult to develop an in vitro model of antigen-specific triggering of antibody synthesis by human peripheral blood mononuclear cells that is independent of exogenous mitogens. In the present study a sensitive and reproducible culture system and enzyme-linked immunosorbent assay have been established wherein antigen alone is used to trigger antigen-specific antibody synthesis by mononuclear cells from subjects immunized to keyhole limpet hemocyanin (KLH). The in vitro antigen-induced anti-KLH response is comparable in magnitude to that induced by pokeweed mitogen, is predominantly IgM in isotype, and is accompanied by a simultaneous increase in polyclonal antibody production. Anti-KLH responses were seen at in vitro KLH concentrations as low as 0.05 microgram/ml. However, concentrations of KLH greater than 5 microgram/ml resulted in profound suppression of the anti-LHL response while continuing to trigger large amounts of total polyclonal immunoglobulin synthesis. This suppression by high concentrations of antigen was also observed in pokeweed mitogen-driven anti-KLH production. These observations are consistent with previous results from the mouse model showing a close association between antigen-specific and polyclonal responses and the phenomenon of antigen-induced, antigen-specific suppression. Thus, an in vitro model of antigen induction of antigen-specific antibody synthesis in human peripheral blood mononuclear cells has been demontrated and should prove useful in exploring the mechanism of human B cell activation and immunoregulation.