AGONISTIC AND ANTAGONISTIC PROPERTIES OF CD40 MAB G28-5 ARE DEPENDENTON BINDING VALENCY

CD40 functional responses can be triggered by binding of mAb G28-5. He re we show that G28-5 induces partial CD40 responses and functions as a partial antagonist of natural CD40 ligand, gp39, by preventing gp39 binding. Fab fragments of G28-5 retain inhibitory activity but lose cr osslinking-dependent stimulatory activity. The synergistic interaction of CD40 signals with PMA or CD20 show differential requirements for C D40 crosslinking and different sensitivity to cyclosporine A, suggesti ng that CD40 receptor may use different effector mechanisms for synerg y with calcium-dependent CD20 signals or with calcium-independent sign als from PMA. Activation of NF-kappa B occurred in RAJI cells by G28-5 or by gp39 treatment, and was CD40 crosslinking-dependent. These resu lts suggest that activation of NF-kappa B is involved in some CD40 rec eptor signals and may be related to CD40 effects on stimulation or inh ibition of apotosis. (C) 1995 Wiley-Liss, Inc.