瑞典卡罗林斯卡学院Gunilla B. Karlsson Hedestam小组在研究中取得进展。他们的论文发现了遗传多样性流感抗体突出了IG种系基因变异的作用，并为人群综合疫苗策略提供了信息。该项研究成果发表在2026年3月26日出版的《免疫学》上。

通过将个体化免疫球蛋白基因分型与来自A型流感血凝素（HA）结合的B细胞的高通量配对链抗体测序相结合，该课题组人员开发了一种称为配对表达抗原受体的个体化单细胞分析（ISCAPE）的技术，该课题组人员证明了B细胞对HA的反应是高度个体的。该团队发现了一种常见的IGHV2-70多态性，这种多态性会损害一类中和性HA头部定向抗体的功能。

此外，课题组人员描述了利用IGHD3-3与多种IGHV基因重组的HA中心干细胞靶向广泛中和抗体，扩大了已知的干细胞抗体库，并强调了抗体基因的种群限制。小组认为，多供体库研究，加上个性化免疫球蛋白基因分型，可以揭示种系编码的功能变异，并有助于减轻疫苗设计中的人群脆弱性。

研究人员表示，具有大流行潜力的流感毒株的经常出现，需要在遗传多样性人群中引起保护性免疫反应的疫苗。一个关键但未被充分研究的因素是免疫球蛋白基因的种系编码变异如何影响中和抗体的发展。

附：英文原文

Title: Genetically diverse influenza antibodies highlight the role of IG germline gene variation and inform population-comprehensive vaccine strategies

Author: Alexandra A. Fischer, Martin Corcoran, Philip J.M. Brouwer, Mark Chernyshev, Rebecca A. Gillespie, Andrea Nicoletto, Johannes R. Loeffler, James A. Ferguson, Ioannis Zygouras, Pradeepa Pushparaj, Alesandra J. Rodriguez, Sanjana Narang, Marit J. van Gils, Xaquin Castro Dopico, Masaru Kanekiyo, Andrew B. Ward, Julianna Han, Gunilla B. Karlsson Hedestam

Issue&Volume: 2026-03-26

Abstract: The regular emergence of influenza strains with pandemic potential necessitates vaccines that elicit protective immune responses across genetically diverse human populations. A critical but understudied factor is how germline-encoded variation in immunoglobulin genes shapes the development of neutralizing antibodies. Here, by combining personalized immunoglobulin genotyping with high-throughput paired-chain antibody sequencing from influenza A hemagglutinin (HA)-binding B cells across four donors, using a technique we developed called individualized single-cell analysis of paired expressed antigen receptors (ISCAPE), we demonstrate that B cell responses to HA are highly individual. We identified a common IGHV2-70 polymorphism that impaired the function of a class of neutralizing HA head-directed antibodies. Furthermore, we described HA central stem-targeting broadly neutralizing antibodies that utilize IGHD3-3 recombined with diverse IGHV genes, expanding the known repertoire of stem antibodies and highlighting antibody gene usage population restrictions. We suggest that multi-donor repertoire studies, coupled with personalized immunoglobulin genotyping, can uncover germline-encoded functional variations and help mitigate population vulnerabilities in vaccine design.

DOI: 10.1016/j.immuni.2026.03.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00113-5