A novel recycling mechanism of native IgE-antigen complexes in human B cells facilitates transfer of antigen to dendritic cells for antigen presentation

Publication date: Available online 23 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): P. Engeroff, M. Fellmann, D. Yerly, M.F. Bachmann, M. Vogel
BackgroundIgE-immune complexes have been shown to enhance antibody and T cell responses in mice by targeting CD23 (FcεRII), the low-affinity receptor for IgE on B cells. In humans, the mechanism by which CD23-expressing cells take up IgE-immune complexes (IgE-IC) and process them is not well understood.ObjectiveTo investigate this question, we compared the fate of IgE-IC in human B cells and in CD23 expressing monocyte-derived dendritic cells (moDCs) that represent classical APCs and we aimed at studying IgE-dependent antigen presentation in both cell types.MethodsB cells and monocytes were isolated from peripheral blood and monocytes were differentiated into moDCs. Both cell types were stimulated with IgE-immune complexes consisting of NIP-specific IgE JW8 and NIP-BSA to assess binding, uptake and degradation dynamics. To assess CD23-dependent T cell proliferation, B cells and moDCs were pulsed with IgE-NIP-Tetanus Toxoid (TT) complexes and cocultured with autologous T cells.ResultsIgE-IC binding was CD23-dependent in B cells and moDCs and CD23 aggregation, as well as IgE-IC internalization, occurred in both cell types. While IgE-IC was degraded in moDCs, B cells did not degrade the complexes but recycled them in native form to the cell surface enabling IgE-IC uptake by moDCs in cocultures. The resulting proliferation of specific T cells was dependent on cell-cell contact between B cells and moDC which was explained by increased upregulation of co-stimulatory molecules CD86 and MHC class II on moDCs induced by B cells.ConclusionOur findings argue for a novel model in which human B cells promote specific T cell proliferation upon IgE-IC encounter. On one hand, B cells act as carriers transferring antigen to more efficient APCs such as dendritic cells, on the other hand, B cells can directly promote DC maturation and thereby enhance T cell stimulation.

Teaser

The here described IgE/CD23-dependent antigen recycling and presentation pathway in B cells may be targeted to regulate T cell responses in IgE-mediated diseases.


http://ift.tt/2iwanPc