在B细胞中早期的辅助反应性表观遗传程序印记了随后的血细胞存活率和幽默免疫的持续时间
Tyler J Ripperger1,2, Lucas J D'Souza1, James F Read1,3
1Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
持久的抗体产生依赖于早期的B细胞表观遗传编程,而不仅仅是血细胞. 在早期B细胞中删除ZBTB20会损害长期的抗体免疫力.
科学领域:
- 免疫学
- 分子生物学
- 表观遗传学
背景情况:
- 抗体生产的持续时间对免疫力至关重要,但人们对其了解甚少.
- ZBTB20是血细胞中的转录因子,被认为能维持抗体的产生.
研究的目的:
- 找出控制持续性体内免疫力的分子程序.
- 研究ZBTB20在维持抗体产生中的作用.
主要方法:
- 没有ZBTB20的老鼠.
- 在免疫接种后对B细胞进行单细胞ATAC测序.
- 用不同的辅助剂和基因删除评估了抗体的产生 (Zbtb20,Irf8).
主要成果:
- 在血细胞中ZBTB20的删除没有影响抗体持续时间.
- 在早期B细胞 (免疫接种后的第一周) 中ZBTB20的删除导致了血细胞的丧失.
- 在ZBTB20缺乏的B细胞中观察到高IRF8和Ets依赖的表观遗传程序.
- 在缺乏ZBTB20的小鼠中切换辅助剂或删除Irf8的抗体反应.
结论:
- B细胞内在的表观遗传程序确立了早期印记耐用抗体的产生.
- 这些表观遗传变化在显著的转录变化和长寿血细胞形成之前发生.
- ZBTB20调节早期B细胞表观遗传程序,对持续的抗体免疫力至关重要.
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