Cross-linking of CD32 induces maturation of human monocyte-derived dendritic cells via NF-kappa B signaling pathway.
Dendritic cells (DC) represent a unique set of APCs that initiate immune responses through priming of naive T cells. Maturation of DC is a crucial step during Ag presentation and can be induced by triggering a broad spectrum of DC surface receptors. Although human DC express several receptors for the Fc portion of IgG which were described to play an important role in Ag internalization, little is known about the effects of IgG or immune complexes on DC maturation. In this study, we show that cross-linking of FcgammaR-type II (CD32) with immobilized IgG (imIgG) can induce maturation of human monocyte-derived DC via the NF-kappaB signaling pathway. IgG-mediated maturation was accompanied by a moderate increase of IL-10 secretion, whereas no IL-12 production was observed. Involvement of CD32 was further supported by experiments with the anti-CD32 mAb, which blocked IgG-triggered DC maturation and cytokine secretion significantly. Furthermore, DC cultivated in the presence of imIgG induced allogeneic T cell proliferation. Because this imIgG-induced maturation was considerably impaired in monocyte-derived DC from systemic lupus erythematosus patients, we suggest that DC, which matured in the presence of immune complexes, may contribute to prevention of pathological immune responses.
Bánki
Zoltán
Z
Institute of Hygiene and Social Medicine, Leopold-Franzens University and Ludwig Boltzmann Institute for AIDS Research, Innsbruck, Austria.
Kacani
Laco
L
Müllauer
Brigitte
B
Wilflingseder
Doris
D
Obermoser
Gerlinde
G
Niederegger
Harald
H
Schennach
Harald
H
Sprinzl
Georg M
GM
Sepp
Norbert
N
Erdei
Anna
A
Dierich
Manfred P
MP
Stoiber
Heribert
H
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D018949:Antigens, CD1 / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D058851:GPI-Linked Proteins; D006680:HLA Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000276:immunology; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D051996:Transcription Factor RelA
D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; D019013:CD40 Antigens; C428200:FCGR3B protein, human; C080568:Fc gamma receptor IIA; D058851:GPI-Linked Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D017452:Receptors, IgG; D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12