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J Allergy Clin Immunol. 2018 Aug;142(2):557-568.e6. doi: 10.1016/j.jaci.2017.09.024. Epub 2017 Oct 23.

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

Author information

1
Department of Rheumatology, Immunology, and Allergology, Inselspital, University Hospital Bern, Bern, Switzerland.
2
Department of Rheumatology, Immunology, and Allergology, Inselspital, University Hospital Bern, Bern, Switzerland; Jenner Institute, University of Oxford, Oxford, United Kingdom.
3
Department of Rheumatology, Immunology, and Allergology, Inselspital, University Hospital Bern, Bern, Switzerland. Electronic address: monique.vogel@dbmr.unibe.ch.

Abstract

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.

KEYWORDS:

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

PMID:
29074459
DOI:
10.1016/j.jaci.2017.09.024

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