IgG-derived Fc down-regulates virus-induced plasmacytoid dendritic cell (pDC) IFNalpha production

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.