6. CD23 mediated immune response
The consequence of CD23 mediated IgE- immune complex processing or trafficking is still not understood in detail. However, it is thought that IgE modulates immune responses to an antigen via CD23, as was shown in mice for antibody and T cell responses (73,80). The mechanism of antigen presentation mediated by CD23 has been referred to as IgE-facilitated antigen presentation (FAP) (Fig. 3). As B cells are antigen presenting cells expressing MHC class II, B cells could potentially also degrade antigen and display peptides on MHC class II for antigen presentation. This was indeed shown using EBV-transformed human B cells which directly present IgE-immune complexes to T cells (45,81–84). However, as previously mentioned, experiments with primary B cells have shown that IgE-immune complexes are protected from degradation. This difference in processing between normal B cells and EBV-transformed cells requires more detailed investigations, in order to better understand the mechanism of immunomodulation. Despite the fact that primary human B cells failed to directly induce T cell proliferation, they are able to transfer the IgE-immune complexes to human dendritic cells to induce T cell proliferation (70). Fittingly, it was shown in mice that IgE-mediated antigen presentation was, though initiated by B cells, ultimately dependent on dendritic cells (73, 85). The mechanism by which antigen could be transferred from B cells to other cell types is not entirely clear. A potential role in CD23-induced IgE or antigen shipping between immune cells could be attributed to exosomes. It was shown that B cell-derived exosomes can play a role in presenting allergen peptides to activate T cells (86,87) (Fig. 3). Independently, it has been described that the CD23 sheddase ADAM10 can mediate sorting of CD23 into B cell-derived exosomes (88,89). The concept of exosome transfer between B cells and dendritic cells has also been put forth in mice (90). The consequence of CD23-mediated T cell proliferation and whether it is pro- or anti-inflammatory in the allergic context has not been resolved yet, and evidence is generally conflicting. In mouse models of allergic asthma it was both postulated that CD23 could positively (91) as well as negatively regulate allergic airway inflammation (92, 93).