title: IgG-derived Fc down-regulates virus-induced plasmacytoid dendritic cell (pDC) IFNalpha production.
abstract: Interferon alpha (IFNalpha) produced primarily by plasmacytoid dendritic cells (pDC) is a potent component of the anti-viral innate immune response, and modulates adaptive immunity. Primary control of IFNalpha production occurs at a cellular level and is highly dependent upon regulatory factors and their products. Recent studies have identified up-regulation of IFNalpha production mediated by the adaptive immune response in the form of immune specific IgG. These studies establish a role for the external control of IFNalpha production. The current work demonstrates that the Fc portion of IgG is a potent inhibitor of IFNalpha produced by pDCs in response to HIV, HSV, and VSV. Fc down-regulation occurs after IFNalpha production can be detected by bioassay, and suggests the existence of late regulatory events in the control of IFNalpha production. Down-regulation of IFNalpha is not caused by Fc-induced necrosis, apoptosis or neutralization of IFNalpha activity. Demonstration of Fc-mediated down-regulation of IFNalpha provides additional evidence of the role of IgG in the regulation of IFNalpha production.
authors.affiliation: Department of Veterans Affairs, Northern California Health Care System, Martinez, CA, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Green
authors.forename: Tom
authors.initials: T
authors.lastname: Lum
authors.forename: Jon A
authors.initials: JA
authors.lastname: Green
mesh_terms: D017209:Apoptosis / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016898:Interferon-alpha / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism*
chemical_list: D007141:Immunoglobulin Fc Fragments; D016898:Interferon-alpha