Sun Liming, Yin Yuanyuan, Cao Yuqing, Chen Chunlei, Guo Yutong, Cai Zeming, Wu Jiarui, Li Qingrun
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
School of Life Science and Technology, ShanghaiTech university, Shanghai 201210, China.
Biophys Rep. 2025 Apr 30;11(2):129-142. doi: 10.52601/bpr.2024.240045.
In this study, we conducted a comprehensive proteomic analysis of B cells from the spleen, mesenteric lymph nodes (mLN), and peripheral blood mononuclear cells (PBMC) in a time-course model of systemic lupus erythematosus (SLE) using female MRL/lpr mice. By combining fluorescence-activated cell sorting (FACS) and 4D-Data-Independent Acquisition (4D-DIA) mass spectrometry, we quantified nearly 8000 proteins, identifying significant temporal and tissue-specific proteomic changes during SLE progression. PBMC-derived B cells exhibited early proteomic alterations by Week 9, while spleen-derived B cells showed similar changes by Week 12. We identified key regulatory proteins, including BAFF, BAFFR, and NFKB2, involved in B cell survival and activation, as well as novel markers such as CD11c and CD117, which have previously been associated with other immune cells. The study highlights the dynamic reprogramming of B cell proteomes across different tissues, with distinct contributions to SLE pathogenesis, providing valuable insights into the molecular mechanisms underlying B cell dysregulation in lupus. These findings offer potential therapeutic targets and biomarkers for SLE.
在本研究中，我们使用雌性MRL/lpr小鼠，在系统性红斑狼疮（SLE）的时间进程模型中，对来自脾脏、肠系膜淋巴结（mLN）和外周血单个核细胞（PBMC）的B细胞进行了全面的蛋白质组学分析。通过结合荧光激活细胞分选（FACS）和4D数据非依赖采集（4D-DIA）质谱技术，我们对近8000种蛋白质进行了定量，确定了SLE进展过程中显著的时间和组织特异性蛋白质组变化。PBMC来源的B细胞在第9周时出现早期蛋白质组改变，而脾脏来源的B细胞在第12周时表现出类似变化。我们鉴定出了参与B细胞存活和激活的关键调节蛋白，包括BAFF、BAFFR和NFKB2，以及以前与其他免疫细胞相关的新型标志物，如CD11c和CD117。该研究突出了不同组织中B细胞蛋白质组的动态重编程，对SLE发病机制有不同贡献，为狼疮中B细胞失调的分子机制提供了有价值的见解。这些发现为SLE提供了潜在的治疗靶点和生物标志物。
