肝硬化患者B淋巴细胞亚群异常改变的临床意义及功能机制研究

肝硬化患者易发生感染，对疫苗应答低下。过往研究显示肝硬化患者循环CD27+记忆性B细胞显著减少，但患者B细胞亚群免疫缺陷的具体表型、机制及影响尚不明确。前期研究中，我们鉴定肝硬化病人的IgM+IgDloCD27+ B细胞（边缘区B细胞，此处称为MZB样细胞）减少最为显著，病人B细胞亚群的活化比率也显著增高。本课题将进一步研究外周和脾脏的B细胞亚群频率、表型、功能和组织分布；利用宏基因组学、RNAseq和免疫组库等技术探索肝硬化B细胞亚群改变的相关机制，揭示B细胞免疫变化对机体抗细菌免疫功能的可能影响。该研究将加深对肝硬化免疫缺陷、脾脏和肝脏相互作用的理解；可为寻找免疫标志物、改善肝硬化体液免疫奠定研究基础。

Patients with liver cirrhosis often show immunodeficiency and lower response to vaccination. Previous studies have revealed the decrease of peripheral CD27+ memory B cells in cirrhotic patients, however, the exact impact of cirrhosis on B cell population structure, B cell function and host anti-microbial immunity is mostly unclear. We identified that IgM+IgDloCD27+ B cells suffered the most loss in cirrhotic patients. Here, we propose to study the relative mechanisms involved in B cell perturbation utilizing several advanced biological techniques, and reveal the influence of perturbed B cell immunity on host defense. This study will increase our understanding of the B cell dysregulation during liver cirrhosis. It may lead to novel immune markers and novel strategies to improve humoral immunity for cirrhotic patients.