Antagonistic interactions between enhancing and suppressor factors that regulate the humoral immune response

Abstract

In assay cultures of normal mouse spleen cells stimulated with sheep erythrocytes (SRBC) on day 0, the addition on day 2 of murine enhancing factor (MEF), purified from supernatants of mixtures of allogeneic lymphoid cells, resulted in significant non-specific augmentation of the haemolytic plaque response. A different supernatant activity, antibody initiation suppressor factor (AISF), generated by specific anamnestic stimulation of spleen cells from mice immunized 7 days earlier with horse erythrocytes (HRBC), was capable of significant inhibition of the anti-SRBC plaque-forming cell response of similar assay cultures when added simultaneously with SRBC on day 0 of a 5-day culture period. The addition of optimal concentrations of both MEF and AISF to SRBC-stimulated spleen cells at the initiation of culture blocked the inhibitory activity of the suppressive mediator. Similarly, the activity of MEF in enhancing both the AISF-specific (anti-HRBC) and non-specific (anti-SRBC) responses was abrogated in the presence of AISF added in optimal amounts with MEF on day 2 of culture. A similar antagonistic interaction between AISF and MEF was observed when each factor was added, at its respective optimal dilution and time, to SRBC-stimulated splenocytes in vitro. Moreover, AISF, a factor derived from antigen-activated T lymphocytes, failed to replace suppressor T-cell function in assay cultures of T-cell depleted mouse splenic B cells. Paradoxically, AISF markedly enhanced the anti-SRBC haemolytic plaque response of such cultures. The addition of graded numbers of T lymphocytes to AISF-treated B-cell cultures also resulted in an augmented humoral immune response. But the target cell of AISF was the macrophage, since the presence of splenic macrophages in the B-cell cultures reconstituted the suppressive activity of the inhibitor. In addition, AISF dramatically increased the number of macrophage-like colony-forming units in bone marrow cultures in vitro. These data are discussed in terms of the delicate balance and possible interactions between effector molecules which, in part, regulate antibody synthesis.