T-Cell Factors That Promote B-Cell Proliferation and Differentiation

Abstract

The goal of this chapter is to summarize and discuss the studies that have sought to understand just how helper T cells help B cells to proliferate and differeniate into antibody-secreting cells by the production of T-cell factors. The studies of Mitchison and others (Mitchison, 1969) showed that effective T-cell help was only delivered to B cells when both T cell and B cell recognized determinants on the same antigen molecule. This observation led to the hypothesis that T-cell help was delivered via an obligatory cell-cell interaction, and it was later shown that such interactions were major histocompatibility complex (MHC) restricted. Our own studies (Dutton et al, 1971) and those of others (Schimpl and Wecker, 1972) showed that in certain experimental models T cells could be replaced by factors contained in culture supernatants of activated T cells. For awhile, there were those who suggested that the latter mechanism represented a special case seen only with erythrocyte antigens or with previously activated B cell. It is now clear that both mechanisms of T-cell help exist. It is thought that some B cells become activated only via direct cell-cell interaction and that others can be affected directly by T-cell factors (Singer et al., 1982). It has been shown that a major fraction of all resting B cells can be driven through activation, proliferation, and differentiation to immunoglobulin secretion solely with the aid of the appropriate soluble agents—antiimmunoglobulin and T-cell culture supernatants (Howard and Paul, 1983). All B cells can be made to respond to the B-cell mitogens, dextran sulfate, and lipopolysaccharide (LPS), in the presence of macrophage-derived factors (Wetzel and Kettman, 1981).