小柯机器人

美国洛克菲勒大学Gabriel D. Victora小组揭示对重复免疫血清抗体响应的分子命运。相关论文于2023年1月16日在线发表于国际学术期刊《自然》。

研究人员引入了一种分子命运方法，其可以差异地检测到源自特定B细胞的特定人群的血清抗体。结果表明，血清对顺序同源促进的反应来自原代组B细胞，而后来又抑制了来自初始B细胞的新抗体反应诱导。这种“原发性成瘾”随着抗原距离的一种功能而急剧减少，从而使用不同病毒糖蛋白重新免疫可产生针对启动变体的表位的从头抗体反应。这项发现对“原始抗原罪”（OAS）的理解以及针对不断发展的病原体的设计和测试具有影响。

据介绍，血清抗体的保护功效是由不同亲和力和特异性的抗原特异性B细胞克隆的相互作用引起的。这些细胞动力学是血清水平现象的基础，例如OAS，这是一种免疫系统的潜在倾向，是在遇到相关抗原时反复依赖于第一个由抗原刺激参与的B细胞从头响应。新的变异的特异性抗体的OAS型抑制可能对快速发展的病毒（如流感和SARS-COV-2）造成障碍。OAS型抑制的精确测量是具有挑战性的，因为细胞和时间的起源不能轻易地归因于循环中的抗体。 因此，其对随后的抗体反应的影响仍然不清楚。

附：英文原文

Title: Molecular fate-mapping of serum antibody responses to repeat immunization

Author: Schiepers, Arin, van t Wout, Marije F. L., Greaney, Allison J., Zang, Trinity, Muramatsu, Hiromi, Lin, Paulo J. C., Tam, Ying K., Mesin, Luka, Starr, Tyler N., Bieniasz, Paul D., Pardi, Norbert, Bloom, Jesse D., Victora, Gabriel D.

Issue&Volume: 2023-01-16

Abstract: The protective efficacy of serum antibody results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as “Original Antigenic Sin” (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, in detriment of inducing de novo responses1-5. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-26,7. Precise measurement of OAS-type suppression is challenging because cellular and temporal origins cannot readily be ascribed to antibodies in circulation; thus, its impact on subsequent antibody responses remains unclear5,8. Here, we introduce a molecular fate-mapping approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that serum responses to sequential homologous boosting derive overwhelmingly from primary cohort B cells, while later induction of new antibody responses from nave B cells is strongly suppressed. Such “primary addiction” decreases sharply as a function of antigenic distance, allowing reimmunization with divergent viral glycoproteins to produce de novo antibody responses targeting epitopes absent from the priming variant. Our findings have implications for the understanding of OAS and for the design and testing of vaccines against evolving pathogens.

DOI: 10.1038/s41586-023-05715-3

Source: https://www.nature.com/articles/s41586-023-05715-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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