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. A receptor ligand pair central to the trans-mission of this signal is CD40, expressed on the surface of B cells, together with CD40L, 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. B cells are sensitive to these cytokines only subsequent to CD40/CD40L-driven DNA synthesis. A downstream mediator of the CD40 signaling pathway, designated CRAF, is a member of an expanding family of proteins that contain a conserved cysteine- and histidine-rich RING finger motif.