The mode of action of "allogeneic supernatant" (the culture supernatant of a 24-hr mixedlymphocyte 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. We used a limiting dilution analysis, 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 thymusdependent 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.The humoral response to a haptenic determinant coupled to a carrier structure (such as a heterologous erythrocyte) involves some cooperative activity between a hapten-specific bone-marrow-derived lymphoid cell (B-cell) whose progeny will eventually synthesize antibody and a carrier-specific thymus-derived lymphoid cell (T-cell) that performs some "helper" function but does not itself make antibody.Abbreviations: ATXBM, adult thymectomized irradiated bonemarrow-reconstituted mouse; B-cell, bone-marrow-derived lymphoid cell; T-cell, thymus-derived lymphoid cell; LPS, lipopolysaccharide W, from Escherichia coli 055:B5; RBC, red blood cells; SRBC, sheep red blood cells; HRBC, horse red blood cells; Tnp, trinitrophenyl; thymus-dependent (-independent) antigen, an antigen, the response to which is severely depleted in (unaffected by) the absence of thymus-derived lymphoid cells; thymusdeprived mice, mice deprived of thymus and thymus-derived cells.
A number of T cell functions were followed in mice after thymectomy in adult life. It was found that T cells involved in these functions could be divided roughly into two subpopulations: one whose activity was relatively long-lived (longer than 20 weeks) and one, relatively short-lived (on the order of a few weeks). In the long-lived class were those T cells involved in the helper function in the primary IgM and IgG responses to SRBC in vivo and in vitro. Priming for the secondary demonstration of helper activity or delayed hypersensitivity specific for SRBC seemed to involve both classes, although the contribution from the short-lived class was greater. These findings are consistent with models for T cell heterogeneity in which a short-lived population of T cells contains precursors distinct from a second long-lived population containing memory cells. Both classes can apparently contribute to a pool of activated effector cells in a process driven by antigenic stimulation.
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