1. To evaluate the effect of primary in vitro antigenic stimulation on a population of immunologically competent cells, a homologous cell transfer system was used, with adult chickens as the spleen cell donors, killed Brucella abortus as the antigen, and newly hatched chicks as the recipients.
2. The distribution of antibody titers in recipients of cells from random donors was bimodal, with about 30 per cent showing no detectable titer and the remainder distributed normally.
3. Variability of titer was reduced significantly in subgroups receiving cells from a single donor, indicating that the primary source of variability was the genetic capacity of discrete cell populations to respond to antigen.
4. In serial passage studies, activity of donor cell populations was lost rapidly: antibody was not demonstrated after the second passage, and the graft versus host reaction (splenomegaly) was not demonstrated after the third passage. Results were similar with in vitro antigenic stimulation at the time of the first passage only and with additional stimulation at the time of subsequent transfers.
5. The thesis that,the homograft reaction of the newly hatched recipients had contributed significantly to the variability in the single transfer studies and to the rapid loss of activity in the serial transfer experiments was confirmed by the results of transfers following alteration of the lymphoreticular system of the host by thorotrast administration, splenectomy, and treatment with 19-nortestosterone during embryogenesis. All three favored the survival and function of transferred cells, raising the average antibody titer and virtually eliminating the no-response category. The inhibition of homograft immunity was most pronounced in the 19-nortestosterone group.