Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cellproliferation and survival

Regulation of B lymphocyte proliferation is critical to maintenance of self -tolerance, and intercellular interactions are likely to signal such regula tion. Here, we show that coligation of either the adhesion molecule ICAM-1/ CD54 or MHC II with CD40 inhibited cell cycle progression and promoted apop tosis of mouse splenic B cells. This resulted from specific blockade of NF- kappaB induction, which normally inhibits apoptosis. LPS- or B cell recepto r (BCR)-induced proliferation was not inhibited by these treatments, and mA b-induced association of CB40 with other B cell surface molecules did not h ave these effects. Addition of BCR or IL-I signals did not overcome the eff ect of ICAM-1 or MHC II on CB40-induced proliferation. FasL expression was not detected in B cell populations. These results show that MHC II and ICAM -1 specifically modulate CD40-mediated signaling, so inhibiting proliferati on and preventing inhibition of apoptosis. (C) 2001 Academic Press.