Resting B cells can be activated and clonally expanded into antibody-producing cells in response to a combination of cell contact and soluble signals provided by primed helper T (Th) cells. While cytokines IL-4 and IL-13 alone are inadequate for B cell activation, contact with Th cells seems to be sufficient for delivery of proliferative signals. CD40 and CD154 (also designated CD40L or TRAP) comprise a receptor ligand pair central to the transmission of this signal. CD40 is expressed on the surface of B cells and CD154 is expressed on activated T cells. In the presence of such stimulus, IL-4 and IL-13 are capable of triggering immunoglobulin class switching and secretion of IgE. CD154 is a 261 amino acid protein that is is expressed as a soluble cytokine as well as a homotrimeric type II transmembrane protein. Its expression is tightly regulated, and abnormal levels of CD154 are associated with the pathogenesis of atheromatous plaque destabilization and thrombotic events. Mutations in the gene encoding for CD154 are implicated in hyper-IgM immunodeficiency syndrome type 1.