Administration of Adenosine Diphosphate-Ribosyl Transferase Antagonist Allows in vivo Control of Anti-Dinitrophenyl Response

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Abstract
3-Methoxybenzamide (3MB) is one of a series of chemical inhibitors of the nuclear enzyme adenosine diphosphate (ADP)-ribosyl transferase (ADPRT), which has been shown to inhibit cell differentiation in vitro, but has no effect on differentiation independent proliferation. Treatment of mice with an optimal concentration of 3MB (20 mg/kg body weight) at or 1 day after dinitrophenyl-keyhole limpet haemocyanin (DNP-KLH) immunisation reduced anti-DNP plaque-forming cell (PFC) numbers to less than 10% of those of control animals. The period for maximum PFC suppression showed a narrow time window relative to immunisation, suggesting that in vivo, as in vitro, 3MB was acting only on those lymphocytes differentiating in response to antigen. Experimental findings showed that it was possible to select for PFC derived from different populations of DNP-responsive lymphocytes by adjusting the time of 3MB treatment relative to immunisation. When 3MB was used with antigen priming, the residual PFC showed a lower average affinity than PFC in mice treated with 3MB 3 days after priming, suggesting a differential selection of those lymphocytes responding either ‘early’ or ‘late’ in the primary immune response.