Activation and regulation of the I kappa B kinase in human B cells by CD40signaling

This study demonstrates that the engagement of CD40 results in the activati on of the recently described I kappa B kinase (IKK) in a human B cell line. The kinase appears to reside within the cell in a cytosolic signalsome com plex consisting of IKK, I kappa B, and an MKP-1-like molecule. While the bi nding of CD154 to CD40 induces the assembly of a CD40-TRAF receptor complex , IKK is not recruited to this complex. Nonetheless, a functional link betw een TRAF2 and IKK activity in B cells is demonstrated by the fact that over expression of TRAF2 constitutively induces IKK activity, NF-kappa B lucifer ase and Fas expression. Synergy in the activation of IKK and NF-kappa B-dep endent gene expression was observed by the simultaneous engagement of the B cell receptor and CD40, establishing an early means for crosstalk between these two B cell activation pathways. This study discusses the sequential b iochemical events that transpire upon CD40 engagement by its ligand in huma n B cells.