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BACKGROUND: IgE-immune complexes (IgE-ICs) 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-ICs and process them is not well understood. OBJECTIVE: To investigate this question, we compared the fate of IgE-ICs in human B cells and in CD23-expressing monocyte-derived dendritic cells (moDCs) that represent classical antigen-presenting cells and we aimed at studying IgE-dependent antigen presentation in both cell types. METHODS: B cells and monocytes were isolated from peripheral blood, and monocytes were differentiated into moDCs. Both cell types were stimulated with IgE-ICs consisting of 4-hydroxy-3-iodo-5-nitrophenylacetyl (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 complexes and cocultured with autologous T cells. RESULTS: IgE-IC binding was CD23-dependent in B cells, and moDCs and CD23 aggregation, as well as IgE-IC internalization, occurred in both cell types. Although IgE-ICs were 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 moDCs, which was explained by increased upregulation of costimulatory molecules CD86 and MHC class II on moDCs induced by B cells. CONCLUSIONS: Our findings argue for a novel model in which human B cells promote specific T-cell proliferation on IgE-IC encounter. On one hand, B cells act as carriers transferring antigen to more efficient antigen-presenting cells such as DCs. On the other hand, B cells can directly promote DC maturation and thereby enhance T-cell stimulation.

Original publication

DOI

10.1016/j.jaci.2017.09.024

Type

Journal article

Journal

J Allergy Clin Immunol

Publication Date

08/2018

Volume

142

Pages

557 - 568.e6

Keywords

B cells, FcεRII (CD23), IgE, IgE-immune complexes, T-cell activation, antigen recycling, moDC, polarization