Dominant Signals Leading to Inhibitor κB Protein Degradation Mediate CD40 Ligand Rescue of WEHI 231 Immature B Cells from Receptor-Mediated Apoptosis

Recently, we demonstrated maintenance of nuclear factor (NF)-κB/Rel factors plays a major role in B cell survival. Treatment of WEHI 231 immature B cells with an Ab against the surface IgM protein (anti-IgM) induces apoptosis that can be rescued by engagement of CD40 receptor. The dramatic decrease in high basal levels of NF-κB/Rel activity induced by anti-IgM treatment led to cell death. CD40 ligand (CD40L) treatment prevented the drop in NF-κB/Rel factor binding by inducing a sustained decrease in inhibitor (I) κB-α and transient decrease in IκB-β protein levels. In this study, we have investigated the regulation of these NF-κB/Rel-inhibitory proteins. In exponentially growing WEHI 231 cells, the IκB-α and IκB-β proteins decayed with an approximate t1/2 of 38 and 76 min, respectively, which was blocked effectively upon addition of the proteasome-specific inhibitor (benzylcarbonyl)-Leu-Leu-phenylalaninal (Z-LLF-CHO). Anti-IgM treatment stabilized IκB-α and IκB-β proteins. CD40L treatment resulted in a dramatic decrease in t1/2 (