近年移植后B细胞稳态在cGVHD中受到关注，但致B细胞稳态失平衡原因及机理知道甚少。B细胞发育与稳态依赖骨髓微环境，MSC是骨髓微环境中重要基质细胞，对B细胞发育与稳态起重要作用，因他具有免疫调节和支持造血成为HSCT研究热点。研究表明移植前放化疗和移植后aGVHD对基质细胞损伤与cGVHD相关，我们前期研究表明第三方骨髓MSC通过降低cGVHD病人BAFF和恢复B细胞稳态而发挥治疗作用。基于这些我们提出cGVHD病人存在骨髓MSC异常是导致B细胞稳态失平衡和cGVHD发生的假说。为验证假说，本项目在cGVHD病人及动物模型中研究：cGVHD骨髓微环境、MSC和B细胞发育与稳态变化；MSC对骨髓微环境、B细胞发育与稳态及cGVHD的影响。通过这项研究揭示：cGVHD病人骨髓MSC是否存在异常；MSC对骨髓微环境、B细胞发育与稳态和cGVHD影响和机理；为MSC防治cGVHD提供理论依据。

B-cell homeostasis in chronic GVHD after allogeneic stem cell transplantation is gaining more and more attentions in recent years. However, the reason and the mechanism of aberrant B-cell homeostasis are unkown. The ontogeny and homeostasis of B cells depend on the bone marrow microenvironment in which MSC is a main cell of stromal cells and plays an important role in the ontogeny and homeostasis of B cells. MSC becomes a research hotspot in HSCT because it can modulate immunity and support hematopoiesis. Studies show that radiation and chemotherapy pre-transplantation and aGVHD post-transplantation might cause damage to stromal cells, which is associated with the development of cGVHD.Our previous research showed that MSC derived from bone marrow of a third-party donor had therapeutic effect on cGVHD by reducing BAFF and restoring B cell homeostasis. Based on these finding, we propose that MSC abnormity of cGVHD patients is associated with aberrant B cell homeostasis and the development of cGVHD. To test this hypothesis, we will explore the changes of bone marrow microenvironment, MSC, ontogeny and homeostasis of B cell; and the effects of MSC on the bone marrow microenvironment, the ontogeny and homostasis of B cells in cGVHD patients and animal models.These studies will show whether the MSC is abnormal in cGVHD patients and the effects that MSC has on the bone marrow microvironment,the B cell ontogeny and homeostasis and cGVHD.The mechanism of that is also explored in these studies.And these studies will provide new scientific basis for developing novel therapy for cGVHD.