Influenza A subtypes are categorized into group 1 and group 2 based on the hemagglutinin (HA) sequence. Owing to the phylogenetic distance of HAs in different groups, antibodies that bind multiple HA subtypes across different groups are extremely rare. In this study, we demonstrated that an immunization with acid-treated HA antigen elicits germinal center (GC) B cells that bind multiple HA subtypes in both group 1 and group 2. The cross-group GC B cells utilized mostly one V_H gene (1S56) and exhibited a sign of clonal evolution within GCs. The 1S56-lineage IgGs derived from GC B cells were able to bind to HA protein on the infected cell surface but not to the native form of HA protein, suggesting the cryptic nature of the 1S56 epitope and its exposure in infected cells. Finally, the 1S56-lineage IgGs provided protection against lethal infection in an Fc-dependent manner, independent of the virus-neutralizing activity. Thus, we identified 1S56-lineage antibodies as a unique stereotype for achieving cross-group influenza specificity. The antigens exposing the 1S56 epitope may be good candidates for broadly protective immunogens.

中文翻译：

---

抵消流感病毒抗原变异的刻板 B 细胞反应。

A 型流感亚型根据血凝素 (HA) 序列分为第 1 组和第 2 组。由于不同组中 HA 的系统发育距离，跨不同组结合多个 HA 亚型的抗体极为罕见。在这项研究中，我们证明了用酸处理的 HA 抗原进行免疫接种会引发生发中心 (GC) B 细胞，这些细胞结合第 1 组和第 2 组中的多种 HA 亚型。跨组 GC B 细胞主要利用一个 V _H基因 (1S56) 并在 GC 内表现出克隆进化的迹象。源自 GC B 细胞的 1S56 谱系 IgG 能够与受感染细胞表面的 HA 蛋白结合，但不能与天然形式的 HA 蛋白结合，这表明 1S56 表位的隐秘性质及其在受感染细胞中的暴露。最后，1S56 谱系 IgG 以 Fc 依赖性方式提供针对致命感染的保护，与病毒中和活​​性无关。因此，我们将 1S56 谱系抗体鉴定为实现跨组流感特异性的独特刻板印象。暴露 1S56 表位的抗原可能是广泛保护性免疫原的良好候选者。