CD40 signaling induces B cell responsiveness to multiple members of the γ chain-common cytokine family

CD40 signaling induces B cell proliferative and differentiation responses that can be modulated by many different cytokines, Cytokines in the IL-2 receptor gamma chain (gamma(c))-common family are known to play an integral role in B cell development. Therefore, we investigated the possibility that CD40 signaling induced a cell responsiveness to multiple gamma(c)-common cytokines and that individual gamma(c)-common cytokines induced distinct a cell responses. a cells were isolated from lymphoid follicles of sheep Peyer's patches (PP) and co-cultured with murine CD40 ligand (mCD40L), CD40 signaling induced PP a cell responsiveness to recombinant human IL-2, IL-4, IL-7 and IL-15, mCD40L-induced B cell growth was enhanced by combining IL-4 with a second gamma(c)-common cytokine and sustained a cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15, gamma(c)-common cytokine responsiveness remained dependent upon CD40 signaling, and removal of mCD40L resulted in B cell differentiation and cell death. Similar proliferative responses to mCD40L and gamma(c)-common cytokines were observed for both immature (ileal) and mature (jejunal) PP a cells. Finally, the capacity of CD40-activated B cells to respond to multiple gamma(c)-common cytokines was analyzed with individual PP a cell clones, All a cell clones displayed similar proliferative responses to IL-2 but quantitatively different responses to IL-4, IL-7 and IL-15, The biological significance of a cell responsiveness to multiple gamma(c)-common cytokines is discussed.