Nuclear factor-kappa B/Rel is apoptogenic in cytokine withdrawal-induced programmed cell death

In the complex microenvironment where they evolve, developing cells undergo rapid programmed cell death (PCD) when cytokines that support them become limiting. The transcriptional mechanisms of cytokine-withdrawal apoptosis a re poorly understood. In this report, we used early B-lymphocyte tissue cul ture and transgenic tells to demonstrate that nuclear factor-kappa B (NF-ka ppa B) promotes apoptosis during cytokine withdrawal-induced PCD, In the pr ogenitor a lymphocyte model FL5.12, whereas NF-kappa B has an antiapoptotic function in response to tumor necrosis factor-alpha, cytokine withdrawal c auses nuclear translocation of NF-kappa B/cRel, where it is apoptogenic. In hibition of NF-kappa B activation delays cytokine withdrawal-induced PCD in both FL5.12 and transgenic early B cells. Additionally, reconstituting a b one marrow microenvironment ex vivo abrogates the differential apoptotic pa ttern between control and transgenic early B cells.