A Third Signal in B Cell Activation Given by TRF

There is a wealth of experimental evidence supporting the idea that T cells have to intervene in the immune response to many antigens to ensure an optimal antibody response (Reviewed in Greaves et al. 1973). We have addressed our work to the question at whicli step of B cell activation this intervention is necessary. An in vitro culture system (Mishell & Dutton 1967) was applied using spleen cells of thie functionally athymic nu/nu mice and heterologous blood cells as antigens. SRBC can operationally be defined as T cell dependent antigens since the IgM immune response in T cell deprived cultures is far from the optimal response obtained in the presence of T cells (Schimpl & Wecker 1970). In an attempt to restore the immune response in T cell deprived cultures with thymocytes we found that allogeneic thymocytes were greatly superior to syngeneic ones (Schimpl & Wecker 1971). Subsequent experiments showed that the effect could be ascribed to a soluble factor produced by allogeneically or Concanavalin A (Con A) stimulated T cells (Schimpl & Wecker 1972, Wecker et al. 1974). Soluble mediators with similar T cell replacing activities have now been described by many different groups (Dutton et al. 1971, Doria et al. 1972, Gorczynski et al. 1972, Feldmann & Basten 1972, Britton 1972, Sjoberg et al. 1972, Gisler et al. 1973, Rubin et al. 1973, Waldmann & Munro 1973, Watson 1973, Kishimoto & Ishizaka 1973, Amerding & Katz 1974), some factors being obtained from T cells, activated by antigen in vivo and incubated with the same antigen in vitro. The assumption imderlying all further considerations is that such mediators are regularly produced upon stimulation of T cells and that they