The repertoire of specificity of lymphoid cells: primary response and antigenic competition in microcultures.

Using a microculture system which permits the survival of very small numbers of active lymphoid cells, the frequency of units of response towards two non-crossing antigens, SRBC and phage phi17, is determined in long term cultures of calf lymph node cells. A much higher frequency, as hitherto reported using mouse spleen cells, is found: about one active unit of response towards either antigen per 8 x 10(3) cells. When microcultures are stimulated with the two antigens, phenomena of antigenic competition occur: a 40% depression of the response to each antigen takes place when the antigens are added simultaneously or when the second antigen is added at a later time within the first 2 days. When the interval between the two stimulations is 3 days, only the response to the first antigen takes place at the same level of frequency as that obtained from cultures which are stimulated only with this antigen. These results support the hypothesis of pluripotentiality of lymphoid cells. Each immunocompetent cell would contain a large repertoire of specificities; triggering with antigen would provoke a two stage differentiation process. The first stage lasting until 48 hours after stimulation would be reversible, whereas the second stage would be irreversible. The latter step would involve the phenomena of specific antibody synthesis. Theoretical implications of these results are discussed.