*Purpose: Fcγ receptors (FcγR) have been proposed to be involved in the pathogenesis of acute rejection (AR) after organ transplantation. However, the mechanisms by which FcγRIIIB mediate this process are still unclear. Previous studies suggested that the FCGR3B gene copy number variation (CNV) is associated with the risk of autoimmune diseases. In this study, we firstly aimed to investigate the association of FCGR3B-CNV with end-stage renal disease (ESRD) and risk of rejection post kidney transplantation. Then we explored the immunological effect of FcγRIIIB on kidney transplant recipient mice.

*Methods: Firstly, FCGR3B gene copy number in ESRD patients and recipients with AR post kidney transplantation were determined by q-PCR. In addition, we established a model of allogeneic kidney transplantation in transgenic mice expressing the uniquely human FCGR3B gene crossed to wild-type C57Bl/6 mice to explore the role and mechanism of FcγRIIIB in AR after renal transplantation. Finally, in vitro experiments were performed to further explore the possible mechanism of FcγRIIIB in AR after renal transplantation.

*Results: Our data showed that the percentage of kidney transplant recipients with high copy number of FCGR3Bgene was significantly lower than that of healthy controls, suggesting that individuals with low copy of FCGR3Bgene are more prone to develop ESRD. Besides, patients with low copy of the FCGR3Bgene are associated with susceptibility to AR following kidney transplantation. In mice, transgenic expression of human FcγRIIIB effectively inhibited the AR and improved the function of the transplanted kidney in a model of allogeneic kidney transplantation. This protective effect was associated with an inhibition of T lymphocytes infiltration and Th1 cell immune response. Finally, we showed that FcγRIIIB cross-linking combined with TNF-α treatment in vitro promoted neutrophil apoptosis and was associated with increased activation of cleaved caspase-8 and caspase-3.

*Conclusions: FcγRIIIB may inhibits renal transplant rejection by inducing neutrophils apoptosis.

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