Membrane and soluble Fc gamma RII/III modulate the antigen-presenting capacity of murine dendritic epidermal Langerhans cells for IgG-complexed antigens

Abstract

Murine dendritic epidermal Langerhans cells (LC) are APC. This implies that LC take up, process, and present Ag to T cells. One way of doing so that could allow Ag internalization is provided by the low affinity receptors for the Fc region of IgG (Fc gamma R), which murine LC are known to express, although their isoform(s) and function(s) have not been defined. By using molecular biology and biochemical approaches, we demonstrated that LC expressed Fc gamma RIIb2 and Fc gamma RIII. Furthermore, LC internalized Fc gamma R by receptor-mediated endocytosis, as observed with gold-labeled anti-Fc gamma RII/III mAb or immune complexes. We demonstrated the biologic relevance of this process by observing that Fc gamma R-mediated Ag internalization improved by approximately 300-fold the Ag-presenting capacity of LC to T cells. Moreover, analysis of cell culture supernatants showed that two forms of soluble Fc gamma R (sFc gamma R) were released by LC: the first most probably was the secreted transmembrane-deleted Fc gamma RII isoform, Fc gamma RIIb3, and the second was a soluble receptor probably derived from the membrane-associated Fc gamma RII/III. The ability of two recombinant forms, corresponding to the two sFc gamma R released by LC, to inhibit Fc gamma R-mediated presentation enhancement was assayed. Preincubation of IgG-complexed Ag with either rsFc gamma R led to a dose-dependent decrease in the Ag-presenting capacity of LC. Taken together, our results suggest that, in vivo, LC express membrane Fc gamma R, which increase their Ag-presenting capacity for IgG-complexed Ag, and release sFc gamma R, which might be able to modulate this Ag presentation.