International Immunology, Vol. 11, No. 7, 1139-1147,
July 1999
© 1999 Japanese Society for Immunology
CD40 signaling induces B cell responsiveness to multiple members of the 
chain-common cytokine family
Veterinary Infectious Disease Organization, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada
1 Institut Bordet, University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium
2 Basel Institute for Immunology, 487 Grenzacherstrasse, Basel 4005, Switzerland
Correspondence to: P. J. Griebel
CD40 signaling induces B cell proliferative and differentiation responses that can be modulated by many different cytokines. Cytokines in the IL-2 receptor 
chain (c)-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 c-common cytokines and that individual c-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 c-common cytokine and sustained B cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15. 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 c-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 c-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 c-common cytokines is discussed.
Keywords: B lymphocytes, CD40, CD40 ligand, chain-common cytokines, IL-2, IL-4, IL-7, IL-15, Peyer's patch, sheep
Transmitting editor: C. J. Paige
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