Regulation of B-Cell Growth and Differentiation by Soluble Factors

Abstract

The B-lymphocyte family of cells presents one of the most remarkable opportunities for the detailed study of regulation of growth and differentiation. Some members of this cell population have the property that they may be stimulated by ligand-receptor interactions, together with the sequential action of a series of lymphokines, to progress from the resting state, through several rounds of proliferation, and then to differentiate to immunoglobulin secretion. Other cells in this group participate in cognate cellular interactions with helper T cells in which the recognition of both antigen and a class II MHC molecule on the B-cell surface is key to activation. The differentiation of these cells is also controlled by soluble products. We have reviewed our developing knowledge of the biochemistry and mode of action of the lymphokines that act upon B cells. These include distinct growth and differentiation factors. Among these are the BCGFs of mice and humans and the various TRFs, which include molecules often described as differentiation factors. The next several years should witness major progress in understanding the physicochemical properties of the B cell-specific factors, their time and nature of action, and the nature of their receptors. In addition, we can anticipate a major effort to understand the intracellular events that flow from the action of specific growth and differentiation factors that act upon B cells. Such information should lead to a new physiologically-based pharmacology for manipulation of antibody responses in human disease and in responses to vaccines. In addition, the fuller understanding of the nature and mode of action of the various growth and differentiation factors should make long-term growth of cloned B cells a procedure that can be routinely used in immunological laboratories for the precise study of the biology of responses by homogeneous populations of B lymphocytes.