Overexpression of RelA causes G(1) arrest and apoptosis in a pro-B cell line

NF-kappa B/Rel family proteins form a network of posttranslationally regula ted transcription factors that respond to a variety of extracellular stimul i and mediate distinct cellular responses. These responses include cytokine gene expression, regulated cell cycle activation, and both the protection from and induction of the cell death program. To examine the function of in dividual Rel family proteins in B cell development and resolve their role i n the signaling of apoptosis, we used a tetracycline-regulated gene express ion system to overexpress either c-Rel or RelA in the transformed pro-B cel l line 220-8. Elevated levels of RelA, but not c-Rel, induced a G(1) cell c ycle arrest followed by apoptosis. Both the DNA binding and transactivation domains of RelA were required for this effect. When RelA was overexpressed in the immature B cell line WEHI 231 or the mature B cell line M12, neithe r cell cycle arrest nor apoptosis was evident. The differential effects of elevated RelA levels in these cell lines suggests that susceptibility to NF -kappa B-induced apoptosis may reflect a relevant selection event during B cell development.