Mechanism of allosuppression: evidence for direct suppression of responding B cells.

The mechanism of allosuppression has been investigated. As previously described, negative allogeneic effects result when T cells recognize MHC-encoded alloantigens on responding lymphocytes, preventing the generation of a secondary anti-PFC response in vitro. Several experiments suggested that this suppression was not due to the generation of cytotoxic effectors. First, effective suppression occurred only when T cells, either unprimed or alloantigen activated, were added during the first 24 hr of the responding culture. Even previously generated cytotoxic effectors were relatively ineffective when added late in the response. Furthermore, no detectable cytotoxic effectors were found in suppressed cultures. The major target of suppression was the responding B cell. Only B cells carrying alloantigens (thus recognized by the T cells) were suppressed; bystander B cells were little affected. Thus allosuppression appears to involve the recognition by T cells of alloantigens on responding B cells and direct suppression of some early event in the development of these B cells into PFC. The responses of primed B cells were found to be preferentially sensitive to the suppressive effects of allo- T cells, whereas the response of unprimed B cells was influenced preferentially by the helper effects of alloantigen-activated T cells. It is possible that the state of differentiation of the B cell may determine the outcome of the interaction with regulatory T cells.