Independently ligating CD38 and Fc gamma RIIB relays a dominant negative signal to B cells

CD38 is expressed on a variety of hematopoietic cells and has a unique enzy matic activity that converts nicotinamide adenine dinucleotide (NAD) into c yclic ADP-ribose (cADPR) and then into ADPR. CD38 is expressed at increasin gly higher levels on B cells at each stage of B cell differentiation, and i s then down-regulated on germinal center B cells and mature plasma cells. C rosslinking of CD38 on the surface of mature, resting B cells induces B-cel l proliferation, which is enhanced by co-signals such as IL-4 and LPS. CD38 -induced proliferation is abrogated by Fc gamma RIIB ligation and this inhi bition can be effected by the addition of anti-Fc gamma RII Ab midway throu gh a 48 h in vitro culture indicating that it delivers a potent negative si gnal to CD38 activated B cells. The suppressive signal was shown to occur t hrough the Fc gamma RIIB because CD38-induced B-cell activation was not inh ibited by the ligation of Fc gamma RIIB in Fc gamma RII-deficient B cells. These results indicate that Fc gamma RIIB can act as a regulatory molecule that modulates CD38 signals in vivo.