Regulated expression of FcgammaR in human dendritic cells controls cross-presentation of antigen-antibody complexes.
Receptors for IgG (FcgammaR) expressed in dendritic cells (DCs) influence the initiation of Ab-mediated immunity. Dynamic variations in FcgammaR expression allow DCs to adjust their capacity to capture Ab-opsonized Ag. The current paradigm predicts a progressive decline in FcgammaR-mediated phagocytic function upon DC maturation. Surprisingly, we find that expression of the phagocytic receptor FcgammaRIIa is preserved in immature and mature DCs at comparable levels with macrophages. Moreover, phagocytosis of antigenic peptides directed to FcgammaRIIa on DCs leads to dramatic increases in Ag cross-presentation and T cell activation. In immature DCs, high expression of inhibitory FcgammaRIIb correlates with decreased uptake and cross-presentation of Ab-Ag complexes. In contrast, engagement of FcgammaRIIb is not associated with changes in cross-presentation in mature DCs. We provide evidence that FcgammaRIIb expression is patently reduced in mature DCs, an effect that is modulated by treatment with cytokines. The regulated expression of activating and inhibitory FcgammaRs in DCs emerges as a critical checkpoint in the process of Ag uptake and cross-presentation.
Liu
Yi
Y
Research Division, Hospital for Special Surgery, Weill Graduate School of Medical Sciences, New York, NY 10021, USA.
Gao
Xiaoni
X
Masuda
Emi
E
Redecha
Patricia B
PB
Blank
Marissa C
MC
Pricop
Luminita
L
D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D003429:Cross Reactions / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C499173:FCGR2B protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG