Donor MHC-specific IgE augments the T and B cell alloresponse in a CD23-dependent manner

The emergence of IgE antibodies specific for donor MHC has been observed in murine transplant models and kidney transplant recipients. While IgE's significance in allergies and other TH2-type diseases is well-documented, its potential role in transplant rejection remains largely unexplored. Besides its involvement in immediate-type allergic hypersensitivity reactions via its high-affinity receptor FcεRI, IgE augments allergen-specific T cell activation and antibody production through its low-affinity receptor FcεRII/CD23, a process termed 'facilitated antigen presentation'. Herein we investigate, whether donor MHC-specific IgE amplifies allo-immune responses in transplantation through CD23-dependant FAP. Upon rejection of a mismatched cardiac allograft, murine recipients exhibited elevated frequencies of FcεRI+ basophils and IgE+CD23+ B cells in blood and spleen, along with increased levels of IgE binding via FcεRI and CD23. In vitro, donor-specific IgE facilitated the binding of donor MHC antigens to B cells. Employing a footpad immunization model, IgE enhanced T cell activation and proliferation and increased the levels of donor-reactive B and germinal center B cells in draining lymph nodes via a CD23-dependent process. These findings reveal that donor-specific IgE amplify the alloresponse by promoting the activation and proliferation of donor-reactive lymphocytes through CD23-dependent mechanisms, uncovering a potential role for IgE in transplant rejection.