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

Abstract

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. A sensitive and reproducible culture system and enzyme-linked immunosorbent assay were established; 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 .mu.g/ml. Concentrations of KLH greater than 5 .mu.g/ml resulted in profound suppression of the anti-KLH response while continuing to trigger large amounts of total polyclonal Ig 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. An in vitro model of antigen induction of antigen-specific antibody synthesis in human peripheral blood mononuclear cells was demonstrated and should prove useful in exploring the mechanisms of human B cell activation and immunoregulation.