法氏囊八肽和法氏囊十一肽对体液免疫系统调节作用及机理研究

Immune regulators play an important role in animal disease prevention. Bursal of Fabricius (BF), as the site of B cell differentiation and proliferation, is the only acknowledged central humoral immune organ. Bursin is the first reported peptide isolated from Bursal, while the other novel bursal-derived active peptides and the mechanism on humoral immune regulation are little reported. In our study, BP8 and BP11 were isolated from BF, which play significant roles in humoral immune response. To investigate the immunomodulatory mechanism of these peptides on immune responses, the marrow B cells models of mice will be established, and then the FACS cell sorting and RNA-sequence will be performed to detect the molecular basis of the novel bursal peptides on B cell development. Furthermore, in view of the important role of BF in the humoral immune system, spleen B cells were isolated from spleen of mice, gene microarray and proteomics will be performed to detect the regulatory mechanisms of the novel bursal peptides on mature B cells. To investigate the interaction of the novel bursal peptides on B cells and T cells, the interaction model of B cells and T cells will be established to detect the antibody response, cytokines and cell subtype. Also, the genome analysis will be performed to detect the mechenism and the target molecule. In this project, these results will elucidate the immunomodulatory mechanism of bursal-derived peptides on the humoral immune system, and will provide a novel insight on new experimental reagents for B cell development and immunopharmacological.

免疫调节剂在动物疫病防控中起到重要作用。法氏囊是目前世界上唯一公认的体液免疫中枢免疫器官，是B细胞分化发育和成熟的场所。法氏囊活性肽在其中起到重要作用，但是，除囊素三肽外，其他新型法氏囊活性肽及其调节体液免疫的机理方面的报道较少。本项目拟以本人从法氏囊中新发现的免疫调节肽 (BP8,BP11)为试验材料，首先采用流式细胞分选及转录组测序等技术，研究其调节骨髓B细胞生成与迁移的分子机制；然后通过脾脏成熟B细胞模型，采用基因芯片和蛋白组学等技术，在基因和蛋白水平上研究其调节成熟B细胞增殖活化的分子机制；最后通过B、T细胞相互作用模型，通过抗体、细胞因子、细胞亚型等方面研究法氏囊活性肽对B细胞与T细胞相互作用的影响及分子机制。本项目研究结果有助于解析新型法氏囊活性肽调节体液免疫的分子机制，并为新型免疫增强剂及疫苗生物佐剂的开发奠定基础。

法氏囊是目前世界上唯一公认的体液免疫中枢免疫器官，是B细胞分化发育和成熟的场所。法氏囊活性肽在其中起到重要作用。本课题以从法氏囊中新发现的免疫调节肽 (BP8、BP11)为试验材料，结合运用生物信息学与细胞生物学等方法，对法氏囊活性肽BP8、BP11调节骨髓B细胞生成与迁移、成熟B细胞增殖活化、B细胞与T细胞相互作用的分钟机制进行了初步研究。结果发现BP8、BP11都能促进骨髓干细胞向B细胞分化。BP8促进pre-B细胞和IMB/MB细胞的增殖，BP11促进IMB/MB细胞的增殖。BP8、BP11同时促进IMB/MB的迁移，调节B细胞分化的关键转录因子与相关信号通路。BP8、BP11促进成熟B细胞的增殖、并调节其抗体产生。BP8通过抑制P53的表达、抑制Caspase-3活性，调节NF-κB binding活性，抑制成熟B细胞凋亡。BP8、BP11通过B、T细胞相互作用，间接调节T细胞活性，提高IL-2、IL-17的表达水平，BP8同时能够调节CD4+CD28+、CD4+CD154+T细胞比例。综合上述结果，本研究为探讨活性肽调节体液免疫的分子机制奠定了工作基础，为下一步开发生物佐剂提供了重要线索。