Cell interactions between histoincompatible T an B lymphocytes. IX. The failure of histoincompatible cells is not due to suppression and cannot be circumvented by carrier-priming T cells with allogeneic macrophages.
Two possible explanations for the failure of primed histoincompatible T and B lymphocytes to cooperate in secondary responses of the IgG antibody class have been investigated in the present study: 1) The possible existence of subtle suppressive mechanisms developing as a consequence of mixing two histoincompatible cell populations; and 2) 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 antigens (i.e., the "altered-self" recognition hypothesis). Absence of suppression has been verified by two different approaches, including: 1) the failure of histoincompatible T cells, even in great excess, to interfere with physiologic cooperation between syngeneic T and B lymphocytes; and 2) 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 has been incicated by an inability to circumvent the requirement for I-region identity by priming T cells with allogeneic macrophagebound antigen even when the latter cells are of identical haploytpe 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 intractions 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 our own data, has 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 we term "adaptive differentiation."