Primary antibody response studied by using inhibitors of nucleic acid synthesis

Inhibitors of nucleic acid synthesis were tested for the effect on the primary antibody response. Antibody formation by adult spleen cells mixed with antigenin vitro and transferred to newborn rabbits was completely suppressed by 6-mercaptopurine administered in the initial phase of antibody induction. The extent of inhibition decreased proportionately to the time interval between cell transfer and treatment with 6-MP. Different sensitivity of immunologically competent cells towards 6-MP at various periods of differentiation and interference of 6-MP with synthesis of specific ribonucleic acid is suggested. Actinomycin D did not show any inhibitory effect on the primary antibody responsein vivo which may be due either to the toxicity of the drug or to some other mechanism of synthesis of immunoglobulins than is known for bacterial proteins. Mitomycin C was also ineffective in suppressing the inductive phase of antibody formation. From results with 6-MP and mitomycin C it is concluded that DNA synthesis and mitotic division are not essential steps in the induction of antibodies.