Abstract
The formation of immune complexes results in activation of the innate immune system and subsequent induction of host inflammatory responses. In particular, the binding of IgG immune complexes to FcgammaR on monocytes triggers potent inflammatory responses leading to tissue injury in disease. We investigated whether activation of monocytes via FcgammaR induced cell differentiation, imparting specific inflammatory functions of the innate immune response. Human IgG alone induced monocytes to differentiate into cells with an immature dendritic cell (iDC) phenotype, including up-regulation of CD1b, CD80, CD86, and CD206. Differentiation into CD1b(+) iDC was dependent on activation via CD64 (FcgammaRI) and induction of GM-CSF. The human IgG-differentiated iDC were phenotypically different from GM-CSF-derived iDC at the same level of CD1b expression, with higher cell surface CD86, but lower MHC class II, CD32, CD206, and CD14. Finally, in comparison to GM-CSF-derived iDC, IgG-differentiated iDC were more efficient in activating T cells in both autologous and allogeneic mixed lymphocyte reactions but less efficient at presenting microbial Ag to T cells. Therefore, activation of FcgammaRI on monocytes triggers differentiation into specialized iDC with the capacity to expand autoreactive T cells that may contribute to the pathogenesis of immune complex-mediated tissue injury.