CD40 and Its Ligand

This chapter focuses on the role of CD40 and its ligand, gp39, as central players in the regulation of B cell growth and differentiation. Reciprocal activation requires the formation of stable physical conjugates between helper T (Th) and B cells and also the sequential and interdependent induction or up-regulation of accessory membrane proteins such as CD40 ligand. The downstream signals transduced by the binding of these proteins to their respective ligand, CD40 on the B cell and CD28/CTLA4 on the T cell, result in the polyclonal, antigen-nonspecific, and MHC-non-restricted activation of both partners. Induction of gp39 expression by activated Th leads to the interaction of GP39 with CD40 on the B cells. This phase of T cell help, termed as the “effector phase” is Class II unrestricted and antigen nonspecific. The role of this ligand-receptor pair in the regulation of B cell memory, somatic mutation, and the germinal center reaction still demands significant attention. More surprising is the evolving role of gp39 in mediating inflammation. The fact that anti-gp39 therapy can all but eliminate T-cell-mediated autoimmune diseases, such as experimental allergic encephalomyelitis, autoimmune oophoritis acute GVHD, and graft rejection, suggests another pivotal role of gp39 in the regulation of cell-mediated immune responses. The expanding tissue distribution of CD40 to endothelial cells, fibroblasts, and other non-immune cells suggests a far broader role of gp39-CD40.