生殖系编码的特异性和B细胞反应的可预测性
Marcos C Vieira1, Anna-Karin E Palm2, Christopher T Stamper3,4
1Department of Ecology and Evolution, University of Chicago, Chicago, United States of America.
PLoS pathogens
|August 25, 2023
概括
生殖线免疫球蛋白等位基因可以影响抗体反应,但不同的进化路径限制了高亲和度的可预测性. 即使有遗传倾向,感染和接种疫苗的结果也因突变和机会而有所不同.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 计算生物学 计算生物学
背景情况:
- 抗体对于对抗HIV,流感和SARS-CoV-2等病原体至关重要.
- 高亲和抗体通常来自具有特定免疫球蛋白等位基因的B细胞.
- 在塑造抗体响应质量的过程中,生殖线等位基因与体质突变的作用受到争议.
研究的目的:
- 为了调查生殖线等位基因或随机突变是否主要决定高亲和抗体的产生.
- 评估基于遗传因素的免疫反应的可预测性.
主要方法:
- 计算机模拟模拟B细胞在选择过程中的进化.
- 实验性感染小鼠的流感病毒.
- 对B细胞受体序列和氨基酸替代的分析.
主要成果:
- 模拟表明,强大的生殖线优势导致跨个体一致的等位基因使用.
- 相比之下,较弱的生殖线优势导致了随着时间的推移不同的等位基因的使用,反映了小鼠的实验发现.
- 没有证据表明在亲和力成熟过程中转向特定氨基酸动机的融合进化.
结论:
- 生殖系编码的特异性可以促进类似的免疫反应,但存在各种各样的进化途径来实现高亲和力.
- 抗体对感染和疫苗接种反应的遗传可预测性受到这些多样化的进化途径的限制.
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