IV . SPECIFIC GENERATION OF A THYMuS - DERIVED ENHANCING FACTOR

Recent experimental evidence has provided strong support for the concept that at least two distinct populations of lymphoid cells cooperate in the production of humoral antibody. Synergism between thymus-derived (T cell) 1 and bone marow-derived (B cell) lymphocytes has been described in the induction of antibody synthesis against heterologous erythrocytes (1-3), serum proteins (4, 5), and hapten-protein conjugates (6-8). Although both participating cell types can respond to specific antigenic stimulation (9, 10), actual synthesis of exportable immunoglobulin is apparently limited to cells of B lymphocyte lineage (11, 12). While T cells therefore do not secrete detectable amounts of antibody, they appear in some cases to facilitate antibody production by B cells. However, the mechanism of interaction between these components is not well defined. We recently demonstrated that augmented immune responses similar to those after reexposure to the same antigen need not be specific (13). Inbred mice were primed with tetanus toxoid (TT); later, their spleen cells were maintained in culture with sheep erythrocytes (SRBC). The addition of TT (the antigen used initially for priming) to these cultures resulted in significant enhancement of the anti-SRBC plaque-forming cell (PFC) response as compared to aliquots cultured without TT. The addition of TT to comparable cultures of spleen cells from normal mice, or the addition of another antigen to TT-primed cultures, failed to produce enhancement of anti-SRBC plaques. Moreover, augmentation of the number of plaques was obtained by adding TT to mixed cultures of normal spleen cells plus thymocytes from TT-primed mice (14). These observations were consistent with the concept, first suggested by Davies et al. (11), that a mediator released from specifically stimulated T cells acts on the antibodyforming B cells to increase their productive response. Supernatants deri~ed from