血细胞分化,抗体质量和初始生殖中心B细胞数量取决于葡萄糖流入率
Shawna K Brookens1,2,3, Sung Hoon Cho1,4,5, Yeeun Paik1
1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.
Journal of immunology (Baltimore, Md. : 1950)
|November 13, 2023
概括
生殖中心 (GC) B细胞需要葡萄糖来进行最佳的抗体生产和血细胞生成. 然而,像银河糖和曼诺糖这样的替代糖可以支持即使没有葡萄糖的抗体分泌,揭示了代谢灵活性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 生物化学 生物化学
背景情况:
- 生殖中心 (GC) 反应对于优化抗体 (Ab) 亲和力和免疫记忆至关重要.
- 在GC反应过程中B细胞的增殖需要大量的营养供应来进行合成代谢.
- 葡萄糖代谢在GCB细胞中的作用一直受到争议,之前的研究表明能量贡献有限.
研究的目的:
- 研究葡萄糖载体1 (GLUT1) 对GCB细胞功能和Ab细胞生产的必要性.
- 阐明GCB细胞所使用的代谢途径,特别是葡萄糖流量.
- 探索在葡萄糖有限条件下支持Ab分泌的替代性赫索索源.
主要方法:
- 使用了一种小鼠模型,在GC启动后GLUT1表达减少.
- 分析了GC B细胞群动态,亲和力成熟和血细胞输出.
- 量化的葡萄糖氧化和流入酸通路 (PPP).
- 在各种赫索索条件下评估反应性氧物种 (ROS) 含量和Ab分泌量 (无葡萄糖与银河糖/曼诺糖).
主要成果:
- 减少GLUT1表达导致GC B细胞数量减少,亲和力成熟受损,血细胞产量降低.
- GC B细胞表现出高水平的葡萄糖氧化,与增加流向PPP,这对于ROS控制和Ab分泌细胞的生产至关重要.
- 虽然葡萄糖的流入对血细胞的产生很重要,但GCB细胞表现出代谢灵活性,而银河糖和曼在无葡萄糖的环境中支持Ab分泌.
结论:
- 通过GLUT1的正常葡萄糖流入对于最佳的GCB细胞反应至关重要,特别是对于血细胞分化和Ab生产.
- 酸途径在管理ROS和支持GCB细胞内的Ab分泌细胞生成方面发挥着关键作用.
- GC B 细胞具有惊人的代谢灵活性,能够利用像银河糖和曼这样的替代性六合酶来维持 Ab 分泌,突出显示了营养利用中的适应性.
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