DNA replication as a prerequisite for the induction of primary antibody response

Abstract

Studies were carried out to test whether the induction of a primary production of antibodies is determined by DNA replication. An in vitro system for the induction of antibody to dinitrophenyl (DNP) determinants following immunization with α-DNP-poly- l-lysine was employed. Cytosine arabinoside (CA), at doses which inhibited DNA synthesis, yet did not affect viability of cells, was applied at different time intervals following antigenic stimulation. Inhibition of DNA synthesis during 36–48 hr following antigenic stimulation prevented the appearance of antibody producing cells. On the other hand, CA applied during the first 36 hr or at 48 hr did not prevent antibody production. Thus, one critical cycle of DNA replication seems to determine antibody production. The lag period prior to the CA-sensitive period is antigen determined. Spleens of animals which were preimmunized with rabbit serum albumin (RSA), then stimulated in vitro with DNP-RSA, showed the same pattern of sensitivity to CA. It is proposed that one cycle of DNA replication is essential for the differentiation of precursor B cells to antibody producing cells. We have previously found that one critical replication determines the carrier effect. A model of the replicating event of T and B cells during the induction of an immune response to hapten-carrier conjugates is suggested.