Antigen Stimulated DNA and RNA Synthesis in Spleen Cell Suspensions from Immunized Rabbits

Abstract

SEVERAL metabolic inhibitors have been shown to inhibit the initiation of antibody synthesis in a variety of in vitro systems (see Table 1), and it has been suggested that certain of these agents may inhibit antibody formation by suppressing the formation of the messenger RNA which directs the synthesis of the antibody molecule, although other explanations have been considered^3,4. In these studies the effect of the inhibitor was assessed after several days' incubation with the cells. Subsequent studies in which much shorter time periods were used have suggested that this may be the case^5,6. It has been shown, however, that the antibody forming cell population arises by a rapid proliferation of a much smaller number of precursor cells, both in vivo^7–9 and in vitro^10–12, in both the primary and secondary response. It is clear that any agent which inhibits such proliferation will reduce the subsequent synthesis of antibody in experiments extended over longer periods of time. It is also probable that specific inhibitors of RNA and protein synthesis will subsequently affect DNA synthesis, providing the time of incubation with the drug is sufficiently prolonged. It was therefore of some interest to measure the concentration of a selected group of metabolic antagonists which would inhibit DNA, RNA and protein synthesis in an appropriate in vitro system. The results of such a study are recorded in Fig. 1.