We have located links that may give you full text access.
A novel recycling mechanism of native IgE-antigen complexes in human B cells facilitates transfer of antigen to dendritic cells for antigen presentation.
Journal of Allergy and Clinical Immunology 2018 August
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.
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.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app