DOCK8免疫缺陷综合征（DIDS）是由DOCK8基因突变引起编码的DOCK8蛋白缺失所致，但其发病机制尚不清楚。我们的前期研究发现DIDS患者的记忆B细胞（MBCs）及构建的DOCK8-/-小鼠的初始B细胞均表现早期激活的障碍。而MBCs在维持免疫记忆中发挥着重要作用，且其早期激活是启动MBCs免疫应答的关键环节。有文献报道在T细胞中DOCK8可促进TCR介导的WAS蛋白（WASp）激活，而WASp是MBCs早期激活的重要调节分子。因此，我们提出假设：DOCK8通过WASp促进MBCs早期激活，进而影响机体体液免疫记忆。本课题拟通过TIRF从患者和小鼠两个方面首先明确DOCK8对MBCs早期激活的影响，进一步通过构建的骨髓嵌合小鼠，从体内和体外研究证实DOCK8通过WASp调控MBCs早期激活的机制。本研究为原创性研究，旨在探讨DIDS免疫缺陷的机制，为临床治疗DIDS提供分子靶标。

DOCK8 immunodeficiency syndrome (DIDS) is caused by the deficiency of DOCK8 protein results from the DOCK8 gene mutations. However, the pathogenesis of the DIDS is not clear. Our previous study has found that the early activation of memory B cells (MBCs) from DIDS patients and naïve B cells from DOCK8-/- mice were inhibited. MBCs play a key role in maintaining humoral immune memory, and the early activation is the first step of immune response of MBCs. It has been reported that DOCK8 enhances the TCR-driven WASp activation in T cells, and WASp is an important regulator of early activation of MBCs. So we speculate that DOCK8 influences humoral immune response by enhancing the early activation of MBCs via WASp. In this project, we first plan to investigate the effects of DOCK8 on the early activation of MBCs in DOCK8 patients and DOCK8-/-mice by TIRF, and then we will study on the mechanism on how DOCK8 regulates the early activation of MBCs in vivo and in vitro by establishing the chimera mice and using the classical methods. The present study is the first time to focus on the mechanism of immunodeficiency in DIDS, and thus may provide a new explanation of DIDS immunodeficiency and some new targets for DIDS treatment.