调节性B细胞（Breg）是一群以分泌IL-10为主的B细胞亚群，近年来成为继调节性T细胞（Treg），自然杀伤性T细胞（NKT）后，细胞免疫调节的新热点。我们前期实验研究发现，Breg与炎症性肠病（IBD）的发生发展及转归密切相关。基于此，本项目拟以葡聚糖硫酸钠（DSS）诱导的小鼠IBD为模型，通过流式细胞检测与分选不同表型的调节性B细胞、体外细胞增殖抑制试验及体内转输功能检测等研究在疾病的不同阶段Breg数量及功能变化；进一步利用基因芯片筛选出与Breg免疫调节密切相关的作用分子，如Breg的转录因子或信号传导分子。在此基础上，以相应的单克隆抗体阻断和基因敲除小鼠等方法深入探讨Breg在IBD炎症微环境下激活分化的方式以及发挥负性调节作用的分子机制，旨在阐明Breg这一新型调节性细胞在IBD发病以及转归中的作用，为炎症性肠病的诊疗提供理论及实验依据。

Regulatory B cells, characterized as a subset of IL-10 producing B cells, are indicated to be a novel player in immunoregulation following regulatory T cells (Tregs) and natural killer T cells (NKT). Based on the observation in our previous study that Breg showed significant association with the development and resolution of inflammatory bowel disease (IBD), this project was designed to take further investigation on the involvement of Breg in IBD. By establishing the murine model of IBD induced by dextran sulfate sodium (DSS), Breg with distinct phenotype will be detected and isolated by Flow Cytometry, while the specific function of Breg in different phases of the disease analyzed by assays such as in vitro cell proliferation inhibition assay and in vivo adoptive transfer. Then, microarray will be employed to screen effector molecules (e.g. transcription factors, signaling transducers) associated with the activation and regulatory function of Breg under the condition of IBD, followed by the confirmation of such mechanism using specific monoclonal antibody blockade assay and genetically engineered mice models. By delineating mechanistically the function of this novel and potent regulator, Breg, in the development and resolution of IBD, this study will provide a basic rationale for the improvement on the diagnosis and treatment of this disease.