从自发生殖中心自主反应的B细胞的动态控制
Kristine Oleinika1, Alexia Correia Ferreira1, Selma Mouftakir1
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
系统性红斑狼涉及自我反应的B细胞. 生殖中心可以取代耐受性,招募无声自反应性B细胞克隆并促进自身抗体多样化.
科学领域:
- 免疫学 免疫学 免疫学
- 这是一种自身免疫力.
- 分子生物学分子生物学
背景情况:
- 系统性红斑狼 (SLE) 涉及产生自身抗体的自我反应性B细胞.
- 混合骨髓嵌合体模型SLE,其中自反应性B细胞向野生型B细胞传播自身免疫力.
- 控制B细胞克隆被纳入生殖中心 (GCs) 的机制尚未完全理解.
研究的目的:
- 调查控制自反应性B细胞克隆纳入GCs的机制.
- 为了确定GC是否可以在SLE的背景下取代外围耐受性.
主要方法:
- 使用CRISPR-Cas9.9生成自动反应性B细胞受体敲进菌株 (M05,G55) 使用CRISPR-Cas9.
- 利用 WT:564Igi 仿真模型研究 B 细胞的行为.
- 分析了自发的GC,自身抗体产生和受体编辑.
主要成果:
- M05和G55小鼠没有自发的GC或自身抗体,受体编辑有助于耐受性.
- 自主反应B细胞 (M05,G55) 与GC结合,并在与564Igi自主反应克隆共存时产生自身抗体.
- GCs 证明了能够招募以前沉默的自动反应B细胞克隆的能力.
结论:
- 生殖中心可以克服外围耐受性机制.
- 自主反应性B细胞克隆,最初是无声的,可以被招募到GC中.
- GCs促进了自身抗体的多样化,有助于SLE的发病.
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