Molecular fate-mapping of serum antibody responses to repeat immunization.
Molecular fate-mapping of serum antibody responses to repeat immunization.
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DOI：
10.1038/s41586-023-05715-3
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发表时间：
2023-03
期刊：
影响因子：
64.8
通讯作者：
Victora, Gabriel D. D.
中科院分区：
文献类型：
--
作者：
Schiepers, Arien;van't Wout, Marije F. L.;Greaney, Allison J. J.;Zang, Trinity;Muramatsu, Hiromi;Lin, Paulo J. C.;Tam, Ying K. K.;Mesin, Luka;Starr, Tyler N. N.;Bieniasz, Paul D. D.;Pardi, Norbert;Bloom, Jesse D. D.;Victora, Gabriel D. D.
血清抗体的保护效力来自于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。这些细胞动力学是血清水平现象的基础，例如“原始抗原性罪恶”（OAS），即免疫系统在遇到相关抗原时反复依赖于由抗原刺激物接合的第一批B细胞的倾向，不利于诱导从头应答。新的变异特异性抗体的OAS型抑制可能对针对快速进化的病毒（如流感和SARS-CoV-2）的疫苗接种构成障碍。OAS型抑制的精确测量是具有挑战性的，因为细胞和时间起源不能容易地归因于循环中的抗体;因此，其对后续抗体应答的影响仍不清楚。在这里，我们介绍了一种分子的命运映射方法，其中血清抗体来源于特定的队列B细胞可以进行差异检测。我们表明，血清反应的顺序同源加强主要来自原代队列B细胞，而后来诱导新的抗体反应的幼稚B细胞强烈抑制。这种“原发性成瘾”作为抗原距离的函数急剧降低，允许用不同的病毒糖蛋白进行再免疫，以产生靶向引发变体中不存在的表位的从头抗体应答。我们的研究结果对理解OAS以及针对不断演变的病原体的疫苗的设计和测试具有影响。
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 responses. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-2. 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 unclear. 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 naïve 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.
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影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
16.8
作者：
Henry C;Palm AE;Krammer F;Wilson PC
通讯作者：
Wilson PC
影响因子：
24.8
作者：
Kuraoka, Masayuki;Yeh, Chen-Hao;Bajic, Goran;Kotaki, Ryutaro;Song, Shengli;Windsor, Ian;Harrison, Stephen C.;Kelsoe, Garnett
通讯作者：
Kelsoe, Garnett
影响因子：
8.8
作者：
Han J;Schmitz AJ;Richey ST;Dai YN;Turner HL;Mohammed BM;Fremont DH;Ellebedy AH;Ward AB
通讯作者：
Ward AB
关于原始抗原罪的歧视。 ii。较低生物的证明。
DOI：
10.1084/jem.124.3.347
发表时间：
1966-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fazekas de St Groth;Webster RG
通讯作者：
Webster RG