肺孢子菌肺炎（PCP）为免疫抑制患者常见的致死性疾病，使用糖皮质激素为患病的主要危险因素。B细胞激活因子受体（BAFFR）对于外周B细胞的存活不可或缺，在感染免疫反应中起重要作用，目前 BAFFR在PCP中的作用机制不详。我们已发现小鼠PCP早期存在BAFFR通路关键基因mRNA表达下调，给予激素的PCP小鼠此现象更为显著，同时外周血及肺组织内B细胞数量下降，提示BAFFR在肺孢子菌感染中可能存在重要作用。本项目将构建野生型、BAFFR-/-及BAFFR过表达PCP小鼠，确定BAFFR缺失对肺孢子菌感染时B细胞、Th细胞功能的影响，阐明其作用机制。此外，通过构建具有上述基因背景的免疫抑制PCP小鼠，明确糖皮质激素对BAFFR通路的作用及激素促进PCP发生发展的机制。本项目的完成有助于加深对PCP免疫机制的认识，了解糖皮质激素导致宿主对肺孢子菌易感的原因，具有重要的科学意义及临床价值。

Pneumocystis pneumonia (PCP) is a life-threatening infectious disease predominantly seen in immunocompromised individuals, which is much more severe in the non-HIV population. B cell activating factor receptor (BAFFR) is indispensable for the survival of periphery B cell and plays a very important role in the host defense against a variety of pathogens. However, the function of BAFFR in PCP is not known currently. In our previous work, we have found a down regulation of mRNA in BAFFR signal pathway related genes in the early period of mice pneumocystis infection and a decrease number of B cell at the same time, with a more significant change in glucocorticoid (GC) treated ones. It is possible that the BAFFR signaling pathway could be important in host defense against PCP. This study will explore the impact of BAFFR on B cell and Th cell generation and differentiation to explain the function of BAFFR in PCP by constructing PCP model in wild-type, BAFFR-/- and BAFFR overexpressed mice. Additionally, by constructing GC-induced immunocompromised PCP model in the type of mice mentioned above, this study will investigate the influence of GC on BAFFR pathway and find out whether GC could promote the development of PCP through BAFFR. This study will deepen the understanding of host immune reaction in PCP, and elucidate the reason why GC increases the risk of PCP, therefore has important scientific significance and clinical value.