作为肌动蛋白聚合的重要因子，WASH (Wiskott-Aldrich Syndrome protein(WASP) and Scar homolog)在T细胞、DC细胞和巨噬细胞中的功能都有报道，但在B细胞中的功能尚属未知。另外，WASH入核参与转录调控的分子机理仍未阐明。我们通过构建B细胞特异性WASH敲除小鼠的研究显示，WASH缺失导致BCR信号和肌动蛋白积累降低、外周B细胞分化异常和免疫应答降低。另外，WASH和pSTAT1存在相互作用，WASH缺失导致pSTAT1降低。但是WASH调控pSTAT1的分子机制和WASH是否和如何通过STAT1调控BCR信号以及后续的B细胞分化和功能尚属未知。本研究将通过特异性敲除和转基因小鼠模型、生化和细胞免疫学方法来阐明上述问题。该研究将最终阐明WASH调控B细胞功能的分子机制，为WASH缺失导致的免疫缺陷、疫苗设计和接种方案优化提供理论基础。

As a critical actin polymerization factor, the function of WASH (Wiskott-Aldrich Syndrome protein(WASP) and Scar homolog) in T cells, DCs and macrophages has been reported. However, its function in B cells is still unknown. Additionally, the molecular mechanism that WASH enters nucleus and involves in the regulation of transcription is not unveiled. Our study by constructing the mouse model with WASH deletion specifically in B cells has shown that the deficiency of WASH leads to the decrease of BCR signaling and actin accumulation, the abnormal B cell differentiation and reduction of immune response. Additionally, WASH interacts with pSTAT1 and the absence of WASH leads to the decrease of pSTAT1. However, the molecular mechanism that WASH regulates pSTAT1, and whether and how WASH regulates the BCR signaling and sequential B cell differentiation and immune response is unknown. Our study is going to use mouse model with gene deletion specifically in B cells and transgenic mouse, biochemistry and cellular immunology method to clarify above issues. This study is going to clarify the molecular mechanism that WASH regulates the function of B cells, and provide theoretical basis for the immunodeficiency caused by the WASH deficiency, vaccine design and optimal vaccination.