Selective activation of antigen-specific human B cells in recently immunized individuals by nonspecific factors in the absence of antigen.

The in vitro effect of nonspecific factors (derived from mixed lymphocyte culture [MLC] supernatants) on human B cell responses was studied in individuals recently immunized in vivo to keyhole limpet hemocyanin, tetanus toxoid, and/or diphtheria toxin. In T cell-depleted fractions of peripheral blood mononuclear cells, nonspecific factors alone, without antigen, selectively induced a specific antibody response to the antigen to which the individual had been recently immunized, at dilutions that did not generate a significant polyclonal response in the remainder of the B cell repertoire. The source of these factors, with respect to MLC donors, did not affect the antibody response. Supernatants of MLC from nonimmunized individuals induced a specific antibody response as effectively as supernatants of MLC from immunized individuals, when added to B cells plus monocytes from recently immunized individuals. Studies in which the same individuals were followed over time showed that these factor-sensitive B cells are seen in the peripheral blood of recently immunized individuals for only a finite period of time. Thus, in vivo immunization with a specific antigen results in the transient appearance in the peripheral blood of B cells that are specific for the antigen in question. These B cells are probably preactivated in that nonspecific factors selectively induce in vitro their further differentiation into antibody-secreting cells, in the absence of added antigen or mitogen. These studies may add further insight into our understanding of the sequential steps involved in the activation and differentiation of human B lymphocytes and provide a model for the combined in vivo and in vitro study of human B cell physiology.