Immunological Tolerance in Bone Marrow-Derived Lymphocytes

Abstract

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.

Immunological Tolerance in Bone Marrow-Derived Lymphocytes

“…However, the efficiency, kinetics, and duration of tolerance induction in vivo has always been of considerably greater magnitude than tolerance induced in vitro in our hands (3). Moreover, data will be presented in the following paper which documents a similar situation with tolerance induced in vivo with immunogenic molecules such as DNP-OVA under proper conditions (18). Finally, it should be pointed out that the experiments presented herein are representative of three-four experiments of each type, which all reproduce these basic observations quite consistently.…”

“…In addition, the fact that DNP-OVA-treated cells were initially unresponsive but could be reversed by trypsinization appeared to point out at least a second distinct type of tolerance mechanism in B cells whereby transient unresponsiveness occurred due to surface receptor "blockade" presumably resulting from the binding of specific determinants by B cells in the absence of a suitable T-cell influence. The latter issue is, indeed, an important one which is considered in greater depth in the accompanying manuscript (18).…”

“…The second category, exemplified by physiological molecules and their analogues (such as DNP-OVA), involves cell surface binding and subsequent unresponsiveness, but the state is clearly reversible by certain maneuvers at least for a finite time, and may or may not either spontaneously reverse itself or develop into irrevocable inactivation. It is with this second category, and the relationship of T-cell function to it, that the following paper will be concerned (18).…”

Genetic Control of Immune Responses in Vitro

“…The increased susceptibility of nonresponder spleen cells to tolerance induction could be explained by the absence of GATspecific helper T-cell function. It has indeed been shown that spleen cells in the absence of activated helper T cells are easily tolerized (14,15). We have also shown that GAT-specific helper function cannot be demonstrated in nonresponder mice immunized with GAT.…”

“…As shown in Fig. 3 and in the accompanying paper (13) It has been demonstrated that B cells are more readily rendered unresponsive by antigens in the absence of specific helper T cells (14,15). Thus, it is possible to argue that the nonresponder B cells in the previous experiment were rendered tolerant to GAT while responder B cells were not, since the responder B cells were influenced by GAT-specific helper cell activity from the F~ T cells, whereas nonresponder B cells may be influenced only by MBSA helper T-cell activity.…”