title: Cytokine-induced immune complex binding to the high-affinity IgG receptor, FcγRI, in the presence of monomeric IgG.
abstract: FcγRI is the sole high-affinity immunoglobulin G (IgG) receptor on leukocytes. Its role in immunity and the clearance of opsonized particles has been challenged, as the receptor function may well be hindered by serum IgG. Here, we document immune complex binding by FcγRI to be readily enhanced by cytokine stimulation, whereas binding of monomeric IgG only modestly increased. Enhanced immune complex binding was independent of FcγRI surface expression levels. FcγRI, saturated with prebound IgG, was found capable of effective immune complex binding upon cytokine stimulation. Cytokine-enhanced binding was observed across a variety of immune complexes, including huIgG3- or mIgG2a-opsonized red blood cells, rituximab- or ofatumumab-opsonized B-cell lymphoma, and cetuximab-opsonized glioblastoma cells. This study contributes to our understanding of how FcγRI can participate in the clearance of opsonized particles despite saturation by monomeric IgG.
authors.affiliation: Immunotherapy Laboratory, Department of Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Cees E
authors.initials: CE
authors.lastname: van der Poel
authors.forename: Roos A
authors.initials: RA
authors.lastname: Karssemeijer
authors.forename: Peter
authors.initials: P
authors.lastname: Boross
authors.forename: Joke A
authors.initials: JA
authors.lastname: van der Linden
authors.forename: Miranda
authors.initials: M
authors.lastname: Blokland
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: Jeanette H W
authors.initials: JH
authors.lastname: Leusen
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004912:Erythrocytes / Q000276:immunology; D005909:Glioblastoma / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D009895:Opsonin Proteins / Q000378:metabolism; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D016207:Cytokines; C489017:FCGR1A protein, human; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D017452:Receptors, IgG