Acidic pH increases the avidity of Fc gamma R for immune complexes

The interaction of immunoglobulin G (IgG) antibodies with Fc gamma R consti tutes a critical mechanism through which IgG antibody effector functions ar e mediated. In the current work we have examined whether human neutrophil F c gamma R exhibit pH dependence in their association with IgG. Binding assa ys were performed in culture medium adjusted to different pH values. It was found that the binding of either heat-aggregated human Ige (AIgG), soluble immune complexes (sIC) or IgG-coated erythrocytes (IgG-E) was markedly hig her at pH 6.5 than at pH 7.3, This effect was not observed when saturation of Fc gamma R was achieved, suggesting that acidic pH increases the avidity of Fc gamma R for IC without modifying the total binding capacity. Similar results were observed for the binding of AIgG to either monocytes, natural killer (NK) or K562 cells, suggesting that acidic pH increases the avidity of both, Fc gamma RII and FcR gamma III. Additional experiments were perfo rmed to analyse whether the binding of IgG to Fc gamma RI also showed pH de pendence. To this aim, we employed interferon-gamma-treated human neutrophi ls and mouse inflammatory macrophages, previously incubated with blocking a ntibodies directed to Fc gamma RII and Fc gamma RIII. Acidic pH did not enh ance the binding of AIgG nor monomeric IgG under these experimental conditi ons. Further studies are required to determine whether the enhancement of F c gamma R avidity for IC could be attributed to titration of histidine(s) r esidues on the Fc fragment of IgC.