Mode of action of a supernatant activity from T cell cultures that nonspecifically stimulates the humoral immune response

The mode of action of 'allogeneic supernatant' (the culture supernatant of a 24 hr mixed lymphocyte reaction), has been studied. This factor stimulates the response of spleen cell cultures depleted in thymus derived lymphoid cells (T cells) to antigens that elicit a thymus dependent response. A limiting dilution analysis was used, in which the frequency and size of response of individual bone marrow derived lymphoid cells (B cells) could be measured. In confirmation of other reports, the occurrence of B cells responding to antigen under different conditions was shown to follow a Poisson distribution in mouse spleen cell suspensions. Allogeneic supernatant increased responses to thymus dependent antigens, both by increasing the frequency of B cells whose response is initiated and by increasing the numbers of antibody forming cells obtained from each responding B cell. Two fractions were obtained by dialysis of the supernatant. The nondialyzable fraction contained factors able to increase both the frequency of B cells responding to sheep erythrocytes, and the size of the responding unit. The dialysate contained factors that were only able to increase the numbers of antibody forming cells obtained per responding B cell from B cells whose response had already been initiated by antigen specific T cells. Since the nondialyzable factors were active in the absence of detectable functional T cells, it was concluded that these factors, produced by T cells, might represent one mechanism whereby T cells cooperate with B cells in the initiation or development of a humoral immune response.