CD40 signaling induces B cell responsiveness to multiple members of the gamma 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 (gammac)-common family are known to play an integral role in B cell development. Therefore, we investigated the possibility that CD40 signaling induced B cell responsiveness to multiple gammac-common cytokines and that individual gammac-common cytokines induced distinct B cell responses. B cells were isolated from lymphoid follicles of sheep Peyer's patches (PP) and co-cultured with murine CD40 ligand (mCD40L). CD40 signaling induced PP B 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 gammac-common cytokine and sustained B cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15. gammac-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 gammac-common cytokines were observed for both immature (ileal) and mature (jejunal) PP B cells. Finally, the capacity of CD40-activated B cells to respond to multiple gammac-common cytokines was analyzed with individual PP B cell clones. All B 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 B cell responsiveness to multiple gammac-common cytokines is discussed.
Griebel
P
P
Veterinary Infectious Disease Organization, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada.
Beskorwayne
T
T
Van den Broeke
A
A
Ferrari
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007082:Ileum / Q000166:cytology; D015847:Interleukin-4 / Q000494:pharmacology; D007583:Jejunum / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D015398:Signal Transduction / Q000276:immunology*
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D023201:CD40 Ligand; D015847:Interleukin-4