Autoradiographic studies on the immune response.I. The kinetics of plasma cell proliferation.

The origin and growth kinetics of plasma cells have been investigated using autoradiographic labeling techniques. Rats immunized once with Salmonella flagella were given a single pulse of H(3)-thymidine 4 or 40 weeks later. 2 hours after the tracer injection, they received a secondary antigenic stimulus. When animals were sacrificed immediately only certain cells from the resting primarily immunized lymph nodes, notably large and medium lymphocytes, were labeled. Subsequent to secondary stimulation, animals were killed at intervals; nearly all the plasma cells formed within the next 5 to 6 days were labeled. They must thus have been the progeny of cells already capable of synthesizing DNA in resting nodes, most probably of large lymphocytes. Plasmacytopoiesis began with little or no lag following secondary immunization, and the number of labeled plasma cells rose exponentially between the 2nd and 4th day, with a doubling time of about 12 hours. Studies of mean grain counts of primitive cells also suggested that the generation time of plasmablasts was 12 hours or less. The hypothesis was proposed that immunological memory depended on the persistence, following primary stimulation, of a continuously dividing stem line of primitive lymphocytes, reactive at all times to further antigenic stimulation.