CELL-INTERACTIONS BETWEEN HISTOINCOMPATIBLE T-LYMPHOCYTES AND B-LYMPHOCYTES .9. FAILURE OF HISTOINCOMPATIBLE CELLS IS NOT DUE TO SUPPRESSION AND CANNOT BE CIRCUMVENTED BY CARRIER-PRIMING T-CELLS WITH ALLOGENEIC MACROPHAGES

Abstract

Two possible explanations for the failure of primed histoincompatible [mouse] T [thymus-derived] and B [bone marrow-derived] lymphocytes to cooperate in secondary responses of the IgG [immunoglobulin G] antibody class were investigated: the possible existence of subtle suppressive mechanisms developing as a consequence of mixing 2 histoincompatible cell populations; and the possible inability of histoincompatible carrier-primed T cells to recognize and/or be induced to function by carrier determinants presented to them in association with foreign MHC [major histocompatibility] antigens (i.e., the altered-self recognition hypothesis). Absence of suppression was verified by 2 different approaches: the failure of histoincompatible T cells, even in great excess, to interfere with physiologic cooperation between syngeneic T and B lymphocytes; and the failure of histoincompatible B cells to interfere with physiologic cooperation between semi-syngeneic F1 hybrid T cells and parental B cells. The unlikelihood of the altered-self explanation for failure of histoincompatible T and B cells to cooperate was indicated by an inability to circumvent the requirement for I-region identity by priming T cells with allogeneic macrophage-bound antigen even when the latter cells are of identical haplotype with the allogeneic B cells employed in the final cooperation assay. These results strongly substantiate the existence of true genetic restrictions in T-B cell interactions in secondary responses to hapten-protein conjugates. The validity of other observations indicating an absence of genetic restrictions in certain circumstances, considered in the context of these data, suggested the possibility that virgin T and B lymphocytes reciprocally influence one another during the course of cell interactions in response to antigenic and/or other signals, a process termed adaptive differentiation.