Soluble Fcγ receptor IIIb alters the function of polymorphonuclear neutrophils but extends their survival

Abstract

We have established that polymorphonuclear neutrophil (PMN)-binding anti-Fcγ receptor IIIb (FcγRIIIb) autoantibodies (autoAb) inhibit the function of these cells but extend their survival. Here, we show that recombinant FcγRIIIb (rFcγRIIIb), as well as purified FcγRIIIb (pFcγRIIIb), deteriorated the PMN adherence and respiratory burst in a dose-dependent manner. Furthermore, rFcγRIIIb and pFcγRIIIb reduced the level of annexin V-binding PMN from 23.6 ± 1.6% to 6.3 ± 1.0 and 11.0 ± 1.0%, respectively, while human serum albumin exerted no effects. Incubation of rFcγRIIIb with those autoAb binding to soluble FcγRIIIb resulted in the attachment of such immune complexes (IC) to the cells, thereby also delaying apoptosis (44.9 ± 5.9 versus 18.0 ± 2.0% annexin V-binding PMN after 16 hours). Soluble FcγRIIIb, in concert with FcγRIIIb/anti-FcγRIIIb IC, produced similar effects in that the percentage of annexin V-binding PMN declined to 16.0 ± 1.9%. It was thus suggested that FcγRIIIb/anti-FcγRIIIb IC inserted the Fc region of their IgG into the membrane FcγRIIIb. Such an interpretation is consistent with our finding that, whereas aggregated IgG and anti-FcγRIIIb, monoclonal Ab prevented membrane FcγRIIIb/IC interaction, neither soluble FcγRIIIb, nor anti-FcγRII did so. We conclude that the function and the life span of PMN are influenced synergistically by soluble FcγRIIIb and anti-FcγRIIIb autoAb.