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The effects of actinomycin D were studied on successive stages of the primary and secondary (anamnestic) anti-Forssman immunoglobulin hemolysin responses induced in rabbits by the antigen, sheep red blood cells. (Fully developed anamnestic reactivity was tested 1.5-2 months after the start of an untreated initial response.) The stages of both responses include induction by antigen, the latent period, the acute rise of hemolysin to peak titer, and the decline afterwards. This antibiotic modified both responses significantly in ways strikingly similar to those produced by large doses of x-rays. It was injected in a sublethal amount (0.08 mg/kg) at selected times before or after a test intravenous injection of 10(8.3) sheep erythrocytes/kg. Given within several days before the antigen, it delayed and depressed peak titer, whereas given during induction and the latent period, it delayed and enhanced peak titer. Given during the acute rise, its effect decreased, and given during the decline after peak titer, it only produced erratic slight rises in titer. It is suggested that delayed and depressed peak titers are associated with both known activities of sublethal doses of actinomycin D, i.e., cytotoxicity and inhibition of RNA synthesis, whereas enhanced peak titers are brought about by the presence of nucleic acid degradation products released by the cytotoxicity of actinomycin D at the critical time of active RNA synthesis in the latent period. Effects of actinomycin D differed quantitatively in the two responses. During the initial response, delayed depression was not apparent as soon and did not last as long, whereas delayed enhancement was more pronounced. In terms of the cells operating in the two responses, the data indicate that immunologically competent initial cells, as compared to memory cells, are more easily stimulated, are not injured as quickly, recover more rapidly, and overcompensate for the injury for a longer time. In addition, in untreated controls, recruitment of immunologically competent initial cells appears to be largely inhibited during induction of memory cells. Otherwise, decline of the secondary response would be less abrupt.

ACTINOMYCIN D BEFORE AND DURING PRIMARY AND SECONDARY ANTI-FORSSMAN IMMUNOGLOBULIN HEMOLYSIN RESPONSES IN RABBITS