CMTM是本室2003年首次报道的基因家族，CMTM7是其成员之一。在已结题国自然基金资助下，我们发现CMTM7是一个新的Rab5调节分子，参与EGFR等膜受体的转运和信号转导；在Cmtm7全身敲除和B细胞特异性敲除小鼠中，腹腔B-1a细胞比例和绝对数显著下降，血清总IgM明显减少，B-1b和B-2细胞没有明显变化。B-1a和B-2细胞表型、功能各异，起始于不同前体细胞，但二者分化过程相似，BCR信号对其发育、生存和功能至关重要。CMTM7在B细胞中高表达，敲除Cmtm7为什么选择性影响B-1a？其通过什么机制调控B-1a细胞？为回答上述问题，本项目将利用Cmtm7的B细胞特异性敲除小鼠，研究CMTM7对B-1a细胞发育、生存、抗体产生的作用；探索其在BCR内化、转运、信号转导中的功能；明确CMTM7在细菌感染中的效应。其顺利实施，将有助于深入了解B-1a细胞的发育、功能调控机制。

CMTM7 is a member of CMTM family, which was firstly reported by our lab in 2003. With support of the Chinese Natural Science foundation, we found that CMTM7 was a novel regulator of Rab5, a protein known to be required for the traffic and signal transduction of EGFR and other receptors. B-1a cells in peritoneal cavity and serum IgM decreased significantly in Cmtm7 knockout mice, while there was no obvious change in B-1b and B-2 cells. B-1a cells and B-2 cells have different phenotypes and functions, and develop from individual progenitors, but they have similar differentiation stages and BCR signal is essential for their development, survival and function. CMTM7 is highly expressed in B cells, why knockout of Cmtm7 only influences B-1a cells, but not B-2 cells? What is the mechanism by which CMTM7 regulates B-1a cells? To answer these questions, we will investigate the influence of CMTM7 on the development, survival and antibody production of B-1a cells; explore the function of CMTM7 during BCR endocytosis, traffic and signaling pathway; clarify its effects on the first line of defense against bacteria with B cell-specific Cmtm7 knockout mice. The implementation of this project will be helpful to understand the mechanism of B-1a cell development and function.