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. A receptor ligand pair central to the transmission 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. Other members of the family include TRAF1 and TRAF2. The latter proteins have been shown to regulate TNF-R2 as well as CD40 signaling through activation of the NFkB family of transcription factors.