威尔康奈尔医学院Patrick C. Wilson小组近日取得一项新成果。经过不懈努力，他们的最新研究探明了儿童B细胞印记效应削弱针对血凝素柄的抗体。相关论文于2026年3月11日发表于国际顶尖学术期刊《自然》杂志上。

为了了解甲型流感病毒主题印记的基础和影响，研究人员对连续首次感染不同H1N1和H3N2流感病毒株后的幼儿B细胞反应进行了表征。儿童有原发性但其他方面与成人相似的B细胞反应。成年B细胞通常与过去的菌株发生交叉反应，这些菌株的免疫球蛋白基因更加刻板和突变，表明存在大量的同亚型印记。在儿童中，在连续异亚型原发性感染后，高达6%的记忆B细胞是H1/H3交叉反应性的，并与高度保守的中央柄表位结合，这是广泛保护性候选疫苗的主要靶点。超过90%的B细胞对印迹H3N2株具有较高的亲和力，导致其宽度减小，对H1N1株的中和效力降低。从机制上讲，印迹H3菌株和受影响的H1菌株在茎表位（D46N）上共享一个残基变化，这是几乎普遍的反应性转移的核心，尽管只有一个原子群不同。总之，流感病毒的印记可以引起对关键保守表位的几乎整个记忆回忆反应的删除性转移。

据介绍，免疫印迹或原始抗原sin是一种现象，免疫系统在随后接触相关的、通常是进化的病原体后优先回忆其最初的反应。尽管它对疫苗开发具有重要意义，但印迹的主题仍不清楚。

附：英文原文

Title: B cell imprinting in children impairs antibodies to the haemagglutinin stalk

Author: Sun, Jiayi, Jo, Gyunghee, Troxell, Chloe A., Fu, Yanbin, Hoezl, Robert, Lv, Huibin, Abozeid, Hassanein H., Teo, Qi Wen, Pholcharee, Tossapol, McGrath, Joshua J. C., Changrob, Siriruk, Nelson, Sean A., Yasuhara, Atsuhiro, Huang, Min, Zheng, Nai-Ying, Chervin, Jordan C., Li, Lei, Fernndez-Quintero, Monica L., Loeffler, Johannes R., Rodriguez, Alesandra J., Huang, Jiachen, Swanson, Olivia M., Balmaseda, Angel, Kuan, Guillermina, Campredon, Lora, Kaitlynn Allen, E., Neumann, Gabriele, Wu, Nicholas C., Kawaoka, Yoshihiro, Krammer, Florian, Mejias, Asuncion, Ramilo, Octavio, Thomas, Paul G., Gordon, Aubree, Ward, Andrew B., Han, Julianna, Wilson, Patrick C.

Issue&Volume: 2026-03-11

Abstract: Immune imprinting1 or original antigenic sin2 is a phenomenon whereby the immune system preferentially recalls its initial response to a related, often evolving pathogen after subsequent exposure. Despite its important implications for vaccine development, the causes of imprinting remain unclear. Here, to understand the basis and impact of imprinting by influenza A viruses, we characterized the B cell responses of young children after consecutive first infections with divergent H1N1 and H3N2 strains of influenza. Children had a primary but otherwise similar B cell response to that of adults. Adult B cells commonly cross-reacted with past strains using more stereotyped and mutated immunoglobulin genes, indicating substantial homosubtypic imprinting. In children, after consecutive heterosubtypic primary infections, up to 6% of memory B cells are H1/H3 cross-reactive and bind to the highly conserved central stalk epitope—a lead target for broadly protective vaccine candidates. Over 90% of these B cells had a higher affinity for the imprinting H3N2 strain, resulting in reduced breadth and neutralization potency against H1N1 strains. Mechanistically, the imprinting H3 strains and affected H1 strains shared a residue change in the stalk epitope (D46N) that was central to the nearly universal shift in reactivity, despite differing by only a single atomic group. In conclusion, imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

DOI: 10.1038/s41586-026-10248-6

Source: https://www.nature.com/articles/s41586-026-10248-6