ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL

Abstract

The suppressing activity of passively transferred antibodies on antibody synthesis against sheep red cells was investigated at the cellular level by the agar-plaque technique developed by Jerne. Humoral antibodies injected prior to the antigen suppressed the appearance of plaque-forming spleen cells producing 19S antibodies completely. Antibodies given during the first 4 days after antigen injection also showed such action, but only after a latency period of 40 hours. The inhibiting efficiency of 7S antibodies was about 100 to 200 times greater than that of 19S antibodies. The results support the conclusion that humoral antibodies inhibit the immune response by removing the stimulus for the proliferation of the antibody producing cells and not by directly depressing antibody synthesis in already committed cells. Passively transferred antibodies inhibited the 7S response if given prior to, or 24 hours after the antigen injection, in analogy with previous results concerning 19S response. In contrast to these previous results on 19S synthesis, antibody transfer had no detectable effect during the early exponential phase of 7S production (5 to 7 days after antigen injection). Only limited inhibition was observed 3 days after the antigen. One possible explanation of this difference is that 7S-producing cells do not divide, or divide at a slow rate. Antigen injection would stimulate the proliferation of 19S-producing cells. Subsequently these would switch to the synthesis of 7S antibodies. These would inhibit the initiation of new 19S-producing cells by combining with the antigen. They would thus suppress the recruitment of their own precursors. A steady state of 7S antibody production by cells with a long lifetime would be the result. This hypothesis ascribes an important regulatory function to 7S antibodies. They would be parts of a feed-back system preventing excessive cell multiplication in response to a single antigen.