Membrane and soluble Fc γ 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 γ 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 γ RIIb2 and Fc γ RIII. Furthermore, LC internalized Fc γ R by receptor-mediated endocytosis, as observed with gold-labeled anti-Fc γ RII/III mAb or immune complexes. We demonstrated the biologic relevance of this process by observing that Fc γ 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 γ R (sFc γ R) were released by LC: the first most probably was the secreted transmembrane-deleted Fc γ RII isoform, Fc γ RIIb3, and the second was a soluble receptor probably derived from the membrane-associated Fc γ RII/III. The ability of two recombinant forms, corresponding to the two sFc γ R released by LC, to inhibit Fc γ R-mediated presentation enhancement was assayed. Preincubation of IgG-complexed Ag with either rsFc γ 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 γ R, which increase their Ag-presenting capacity for IgG-complexed Ag, and release sFc γ R, which might be able to modulate this Ag presentation.