Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

Transplantation of an autologous or syngeneic graft will not trigger a rejection 32 . However, with a xenogeneic graft, where the donor and recipient are genetically different, the recipient will develop graft rejection 38 . The transfer of mature bat lymphoid cells was expected to cause the development of symptoms related to graft rejection. However, it was surprising to observe that the transplantation of bat cells did not develop any signs of graft rejection in bat-mice even 40 weeks after initial cell injection. To investigate if bat cells would generate a rejection response in NSG mice, bat splenocytes (1 × 10 6 ) were used for transplantation, as majority of the cells within this organ are mature immune cells 38, 43 . Forty weeks after injection, mice appeared healthy with no signs of graft rejection observed. Monocytes, T/NK cells, B cells and DCs were present in NSG mice engrafted with bat splenocytes (Fig. 2a) . The reconstitution levels of bat immune cells in these mice ranged from ~12% to 15% (Fig. 2b) were ~60% to 65%, ~30% to 38%, ~5% to 10% and ~0-1% respectively in peripheral blood (Fig. 2c) . The successful reconstitution with bat splenocytes suggested that bat mature immune cells might have the ability to expand and subsequently lead to long-term in vivo repopulation. This novel finding has never been observed before in species such as, humans, mice and other mammals, which had been tried in such studies [34] [35] [36] 38, [43] [44] [45] [46] [47] [48] [49] .