在量化亲和关系的景观上重复生殖中心进化
William S DeWitt1,2, Ashni A Vora3, Tatsuya Araki3,4
1Department of Genome Sciences, University of Washington, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
生殖中心 (GC) B细胞进化通过累积选择和体性突变 (SHM) 偏差来塑造抗体亲和力. 幸存者偏见扭曲了我们对GC进化动态和随时间推移的亲和关系进展的理解.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 在生殖中心 (GCs) 中的抗体亲和力成熟对适应性免疫至关重要.
- 控制这一过程的进化动态,特别是竞争和选择的作用,尚未完全理解.
研究的目的:
- 描述GCs中抗体亲和力成熟的动态进化特征.
- 研究如何选择和体质突变 (SHM) 塑造GC B细胞进化.
- 了解幸存者偏见对感知亲和关系进展的影响.
主要方法:
- 开发了一种实验进化模型,以重复模拟GC反应.
- 利用深度突变扫描来赋予单个B细胞的亲缘关系.
- 使用时间校准模型来分析进化轨迹.
主要成果:
- 通过累积不完美的选择,GC可以实现可预测的进化结果.
- 身体突变 (SHM) 向偏差显著塑造了进化格局.
- 幸存者偏见扭曲了抗体亲和力随时间的明显进展,解释了诸如对低亲和力血统的宽容和早期平稳等现象.
结论:
- 在GCs中抗体亲和力的进化轨迹是累积选择在SHM偏差影响的景观上作用的结果.
- 显而易见的GC进化的特征在很大程度上是由生存偏见所塑造的,需要仔细解释亲和关系进展数据.
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