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Differential Effects of IL-15 and IL-21 in Myeloid (CD11b+) and Lymphoid (CD11b−) Bone Marrow Cells1

IL-15 has been found to activate NF-κB in various types of cells. However, the role of this transcription factor in IL-15- and IL-21-stimulated murine bone marrow (BM) cells is unclear. In this study, we demonstrated that both IL-15 and IL-21 are capable of delaying BM cell factor deprivation-induced apoptosis, but only IL-15 induced their proliferation. Following separation of BM cells into myeloid (CD11b+) and lymphoid (CD11b−) cell populations, we found that IL-15, but not IL-21, significantly induced proliferation in both cell populations. Both cytokines significantly delayed apoptosis, but only in CD11b− BM cells. IL-15Rα, CD122 (IL-2/15Rβ), and common γ-chains (CD132) were expressed in both populations, whereas IL-21Rα was expressed only in CD11b− BM cells. In addition, we demonstrated that IL-15-induced BM cell proliferation was significantly inhibited in NF-κBp50−/− mice when compared with littermate controls. The ability of IL-15 and IL-21 to delay BM cell apoptosis was slightly inhibited in NF-κBp50−/− mice, whereas the antiapoptotic effect of LPS was markedly reversed. We conclude that IL-15, but not IL-21, induces BM cell proliferation and that both cytokines delay BM cell apoptosis. These biological activities were preferentially observed in CD11b− BM cells. Using NF-κBp50−/− mice, we demonstrated for the first time that NF-κB plays a greater role in IL-15-induced cell proliferation than in IL-15- and IL-21-induced suppression of apoptosis.