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B Signaling Pathway1
* Institute of Hygiene and Social Medicine, Leopold-Franzens University and Ludwig Boltzmann Institute for AIDS Research, Innsbruck, Austria;
Laboratory of Immunotherapy, Department of Otorhinolaryngology and
Central Institute for Blood Transfusion and Division for Immunology, University Hospital, Innsbruck, Austria;
Department of Dermatology and
¶ Institute of Pathophysiology, Medical School, University of Innsbruck, Innsbruck, Austria; and
|| Department of Immunology, Eötvös Loránd University, Budapest, Hungary
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 Fc
R-type II (CD32) with immobilized IgG (imIgG) can induce maturation of human monocyte-derived DC via the NF-
B 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.
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