Factors Affecting B-Cell Growth and Differentiation

Since the discovery of T-B interactions in the antibody response, the mechanism of the regulatory functions of T cells in the B-cell response has been studied extensively in immunology. The possibility that helper functions of T cells may be mediated by soluble products released from T cells was originally proposed by Dutton and his colleagues in 1971 (1). In their experiment with murine splenic B cells, they showed that anti-SRBC (sheep red blood cell) response in T cell-depleted splenic lymphocytes could be reconstituted by culture supernatants of mixed lymphocyte reactions. This was confirmed by Schimpl & Wecker (2) and several other investi­ gators (3-5) who showed the active soluble factor(s) in culture supernatants of mitogens or antigen-stimulated T cells. Schimpl & Wecker demonstrated that cell-free supernatants from alloantigen-stimulated or concanavalin A (Con A}-stimulated T cells could fully substitute for T cells in the response in vitro to unrelated antigens such as SRBC. They postulated that T cells stimulated by their specific antigen released a substance, T cell-replacing factor (TRF), which was able to stimulate B cells to proliferate and/or differentiate only when B cells carried antigens on their receptors. Essentially the same result was reported by Kishimoto & Ishizaka with rabbit B cells (3). They demonstrated that anti-DNP (dinitrophenyl) antibody response could be induced in DNP-primed B cells by the stimulation with DNP-heterologous carrier conjugate and a cell-free supernatant from carrier-primed T cells stimulated with the primed carrier antigen. In a series of experiments, they also demonstrated that the factor(s)