血细胞分化,抗体质量和初始生殖中心B细胞群体取决于葡萄糖流入速率
bioRxiv : the preprint server for biology
|September 25, 2023
概括
生殖中心B细胞对于抗体生产和亲和力成熟至关重要地依赖葡萄糖. 然而,当葡萄糖缺少时,替代糖可以支持抗体分泌和血细胞发育.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
背景情况:
- 生殖中心 (GC) 反应通过B细胞的增殖和选择优化抗体 (Ab) 亲和力.
- B细胞的克隆扩张需要营养供应以进行合成.
- 之前的研究质疑了GC B细胞中葡萄糖吸收和糖解的作用.
研究的目的:
- 研究葡萄糖载体GLUT1在GCB细胞功能中的作用.
- 确定葡萄糖代谢如何影响B细胞增殖,亲和力成熟和抗体分泌.
- 探索 GC B 细胞对黑色素利用的代谢灵活性.
主要方法:
- 在建立B细胞谱之后,GLUT1的消除.
- 分析GCB细胞群体大小,亲和力成熟度和血细胞输出.
- 测量葡萄糖氧化和流入酸通路 (PPP) 的流量.
- 评估反应性氧物种 (ROS) 和抗体分泌细胞 (ASC) 的产生.
- 使用无葡萄糖条件的实验操纵,使用替代的糖糖 (银糖和曼糖).
主要成果:
- 消除GLUT1降低了GCB细胞数量,亲和力成熟和血细胞 (PC) 输出.
- GC B细胞表现出高水平的葡萄糖氧化,主要通过PPP.
- 对于控制ROS和ASC生产,PPP活动至关重要.
- 在缺乏葡萄糖的情况下,银糖和曼糖支持了强大的ASC生产和Ab分泌.
- 葡萄糖流入对于GC恒温和PC生产至关重要,但代谢灵活性存在.
结论:
- 葡萄糖的流入对GC恒温,亲和力成熟和抗体分泌细胞生成至关重要.
- 血细胞的发育依赖于Pentose酸盐途径来实现氧化还原平衡.
- 替代性糖可以支持血细胞的发育和抗体分泌,而不依赖于葡萄糖.
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