Differential effects of anti-Fc gamma RIIIb autoantibodies on polymorphonuclear neutrophil apoptosis and function

Anti-Fc gamma receptor IIIb (Fc gamma RIIIb) human autoantibodies (Ab) have been classified previously into three groups, based on the results of an i ndirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent as say (ELISA): IIF+/ELISA+ (group A), IIF+/ELISA- (group B), and IIF-/ELISA(group C) sera. In this study, differential effects between IIF+ autoAb, re cognizing cell-bound Fc gammaR, and those ELISA+, recognizing only cell-fre e Fc gammaR, were studied on polymorphonuclear neutrophils (PMN). Neither g roup A nor B autoAb was cytotoxic, although both prolonged the survival of PMN by delaying spontaneous apoptosis. By the same extent, the PMN-binding antisera stimulated the appearance of a CD11b(dim) population, following a 12-h incubation. This event was associated with a lowered expression of bet a2 integrin molecules, resulting in altered PMN function. Treatment with gr oups A and B autoAb reduced adhesiveness and respiratory burst. This impair ment of the responses was more pronounced when the cells originated from do nors NA1+NA1+ rather than donors NA2+NA2+, From our observations, the influ ences of anti-Fc gamma RIIIb autoAb on PMN survival, as web as function and subsequent dysregulation of the inflammatory response, have proven somewha t dependent on their target antigens, as determined by IIF coupled with ELI SA and Fc gamma RIIIb polymorphism.