title: Dominant expression of the inhibitory FcgammaRIIB prevents antigen presentation by murine plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) are key regulators of the innate immune response, yet their direct role as APCs in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither up-regulated costimulatory molecules nor activated Ag-specific CD4(+) and CD8(+) T cells. The inability of murine pDCs to promote T cell activation was due to inefficient proteolytic processing of internalized ICs. This defect in the IC processing capacity of pDCs results from a lack of activating FcgammaR expression (FcgammaRI, III, IV) and the dominant expression of the inhibitory receptor FcgammaRIIB. Consistent with this idea, transgenic expression of the activating human FcgammaRIIA gene, not present in the mouse genome, recapitulated the human situation and rescued IC antigenic presentation capacity by murine pDCs. The selective expression of FcgammaRIIB by murine pDCs was not strain dependent and was maintained even following stimulation with TLR ligands and inflammatory cytokines. The unexpected difference between the mouse and human in the expression of activating/inhibitory FcgammaRs has implications for the role of pDCs in Ab-modulated autoimmunity and anti-viral immunity.
authors.affiliation: Department of Medicine and Microbiology, Columbia-Presbyterian Medical Center, Columbia University, New York, NY 10032, USA.
authors.forename: Marcella
authors.initials: M
authors.lastname: Flores
authors.forename: Dharmesh D
authors.initials: DD
authors.lastname: Desai
authors.forename: Matthew
authors.initials: M
authors.lastname: Downie
authors.forename: Bitao
authors.initials: B
authors.lastname: Liang
authors.forename: Michael P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Steven E
authors.initials: SE
authors.lastname: McKenzie
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG