Abstract
IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4+ T cell responses in vivo. The effects require the presence of CD23 (Fcε-receptor II)+ B cells, which capture IgE-complexed antigens (Ag) in the circulation and transport them to splenic B cell follicles. In addition, also CD11c+ cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. To elucidate the nature of this dendritic cell, mice were immunized with ovalbumin (OVA)-specific IgE and OVA, and different populations of CD11c+ cells, obtained from the spleens four hours after immunization, were tested for their ability to present OVA. CD8α− conventional dendritic cells (cDCs) were much more efficient in inducing specific CD4+ T cell proliferation ex vivo than were CD8α+ cDCs or plasmacytoid dendritic cells. Thus, IgE-Ag complexes administered intravenously are rapidly transported to the spleen by recirculating B cells where they are delivered to CD8α− cDCs which induce proliferation of CD4+ T cells.
Highlights
IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4+ T cell responses in vivo
When this was tested experimentally, several lines of evidence suggested that CD11c+ cells and not CD23+ B cells presented IgE-complexed Ag to CD4+ T cells in vivo[7]: (i) IgE-Ag complexes did not induce proliferation of CD4+ T cells in mice where CD11c+ cells were depleted; (ii) spleen cells from mice immunized with IgE-Ag complexes in vivo could only stimulate T cell proliferation ex vivo if they contained CD11c+ cells while depletion of B cells did not abolish the Ag-presenting capacity; (iii) T cell proliferation in CD23−/− mice, immunized with IgE-Ag, could be rescued by transfer of MHC-II-incompatible CD23+ B cells which would be able to transport, but not to present, antigenic peptides to T cells in the recipient mice
It extends and confirms the finding that recirculating B cells rapidly transport IgE-complexed Ag to splenic follicles where the amount of Ag peaks 2–4 h after immunization. It demonstrates that CD8α− conventional dendritic cells (cDCs), but not CD8α+ cDCs or plasmacytoid dendritic cells (pDCs), obtained from mouse spleens 4–8 h after immunization with IgE-OVA induce proliferation of OVA-specific CD4+ T cells ex vivo
Summary
IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4+ T cell responses in vivo. CD11c+ cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. Are not considered professional antigen presenting cells (APCs) but can prime CD4+ T cells or cross-prime CD8+ T cells under certain conditions[24,25,26] They are more well-known for producing high levels of type I interferon after viral infections[25,27,28]. The results show that CD8α− cDCs are the most important APCs in this situation
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