To analyze the interaction between macrophages and splenic lymphocytes with reference to time and concentration, the Mishell-Dutton system was divided into two experimental steps. Step 1 consisted of the cocultivation of spleen cells with various doses of macrophages for different periods of time, while in step 2 macrophages were removed, spleen cells transferred to fresh petri dishes and cultivated until plaque assay. Cocultivation of spleen cells with high doses of macrophages for 4--8 h markedly enhanced the DNA synthesis and plaque-forming cell (PFC) response of sheep red blood cell-stimulated and unstimulated cultures. A cocultivation longer than 24 h resulted in an inhibition of both DNA synthesis and PFC response of spleen cells. These studies suggest a nonspecific function of macrophages on proliferation and differentiation processes in antibody formation.
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