title: Acidic pH increases the avidity of FcgammaR for immune complexes.
abstract: The interaction of immunoglobulin G (IgG) antibodies with FcgammaR constitutes a critical mechanism through which IgG antibody effector functions are mediated. In the current work we have examined whether human neutrophil FcgammaR exhibit pH dependence in their association with IgG. Binding assays were performed in culture medium adjusted to different pH values. It was found that the binding of either heat-aggregated human IgG (AIgG), soluble immune complexes (sIC) or IgG-coated erythrocytes (IgG-E) was markedly higher at pH 6.5 than at pH 7.3. This effect was not observed when saturation of FcgammaR was achieved, suggesting that acidic pH increases the avidity of FcgammaR 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, FcgammaRII and FcgammaRIII. Additional experiments were performed to analyse whether the binding of IgG to FcgammaRI also showed pH dependence. To this aim, we employed interferon-gamma-treated human neutrophils and mouse inflammatory macrophages, previously incubated with blocking antibodies directed to FcgammaRII and FcgammaRIII. Acidic pH did not enhance the binding of AIgG nor monomeric IgG under these experimental conditions. Further studies are required to determine whether the enhancement of FcgammaR avidity for IC could be attributed to titration of histidine(s) residues on the Fc fragment of IgG.
authors.affiliation: Laboratory of Immunology, Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: D H
authors.initials: DH
authors.lastname: López
authors.forename: A S
authors.initials: AS
authors.lastname: Trevani
authors.forename: G
authors.initials: G
authors.lastname: Salamone
authors.forename: G
authors.initials: G
authors.lastname: Andonegui
authors.forename: S
authors.initials: S
authors.lastname: Raiden
authors.forename: M
authors.initials: M
authors.lastname: Giordano
authors.forename: J R
authors.initials: JR
authors.lastname: Geffner
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011485:Protein Binding; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D017452:Receptors, IgG