Factors and events in the activation, proliferation, and differentiation of B cells.

The cellular and biochemical pathways of B-cell activation and the role of antigen presentation by B cells are reviewed. It appears that B cells may be activated by two cellular pathways, one of which is MHC restricted, involving cognate recognition between antigen-presenting B cells and T cells. A second pathway proposed by others is MHC unrestricted and does not involve cognate T/B-cell recognition, with the initial signal to the B cell given by antigen alone. Subsequent to antigen activation, both pathways are driven by nonspecific factors derived from T cells and accessory cells. It is most likely that the MHC-restricted pathway is the major one used in in vivo antibody responses. The pathways used by T-dependent and -independent antigens are also examined. Phospholipid metabolism and Ca2+ mobilization occur following activation of B cells similar to events occurring following activation of other eukaryotic cells. The mechanism and cellular events involved in the induction of antigen-specific immunological tolerance and the possible role of lymphokines in the tolerant state are also discussed. The effects of two extrinsic B-cell activators are presented, one being the Fc fragment of immunoglobulin and its peptides, and the other derivatives of one of the building blocks of nucleic acids. In the former case, small peptides generated from the Fc fragment of immunoglobulin supply differentiating signals to previously activated B cells in the presence of T cells. In the latter case, a family of derivatized guanosine compounds which act both as intracellular mitogens driving B cells to proliferation and immunoglobulin secretion and as potent adjuvants are discussed in detail. These derivatized nucleosides act predominantly on a population of mature B cells which synergize with T-cell lymphokines, and react to a lesser extent with a subpopulation of immature B cells.