Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions
Open Access
- 1 October 2005
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 115 (10), 2914-2923
- https://doi.org/10.1172/jci24772
Abstract
Human monocyte-derived DCs (moDCs) and circulating conventional DCs coexpress activating (CD32a) and inhibitory (CD32b) isoforms of IgG Fcγ receptor (FcγR) II (CD32). The balance between these divergent receptors establishes a threshold of DC activation and enables immune complexes to mediate opposing effects on DC maturation and function. IFN-γ most potently favors CD32a expression on immature DCs, whereas soluble antiinflammatory concentrations of monomeric IgG have the opposite effect. Ligation of CD32a leads to DC maturation, increased stimulation of allogeneic T cells, and enhanced secretion of inflammatory cytokines, with the exception of IL-12p70. Coligation of CD32b limits activation through CD32a and hence reduces the immunogenicity of moDCs even for a strong stimulus like alloantigen. Targeting CD32b alone does not mature or activate DCs but rather maintains an immature state. Coexpression of activating and inhibitory FcγRs by DCs reveals a homeostatic checkpoint for inducing tolerance or immunity by immune complexes. These findings have important implications for understanding the pathophysiology of immune complex diseases and for optimizing the efficacy of therapeutic mAbs. The data also suggest novel strategies for targeting antigens to the activating or inhibitory FcγRs on human DCs to generate either antigen-specific immunity or tolerance.This publication has 49 references indexed in Scilit:
- Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells Is Maintained by Granulocyte/Macrophage Colony-stimulating Factor Plus Interleukin 4 and Downregulated by Tumor Necrosis Factor alphaThe Journal of Immunology, 2018
- Mature myeloid dendritic cell subsets have distinct roles for activation and viability of circulating human natural killer cellsBlood, 2005
- FcγRIIb Balances Efficient Pathogen Clearance and the Cytokine-mediated Consequences of SepsisThe Journal of Experimental Medicine, 2004
- Differential binding to human FcγRIIa and FcγRIIb receptors by human IgG wildtype and mutant antibodiesMolecular Immunology, 2003
- Two Immunoglobulin G Fragment C Receptor Polymorphisms Independently Predict Response to Rituximab in Patients With Follicular LymphomaJournal of Clinical Oncology, 2003
- Expression of Fcγ receptors type II (FcγRII) in chronic lymphocytic leukemia B cellsBlood, 2003
- Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic CellsThe Journal of Experimental Medicine, 2002
- IgG Fc ReceptorsAnnual Review of Immunology, 2001
- A New Set of Monoclonal Antibodies Against Human FcγRII (CD32) and FcγRIII (CD16): Characterization and Use in Various AssaysHybridoma, 1997
- Cytoplasmic Domain Heterogeneity and Functions of IgG Fc Receptors in B LymphocytesScience, 1992