Stereotyped B-cell response that counteracts antigenic variation of influenza viruses
Stereotyped B-cell response that counteracts antigenic variation of influenza viruses
复制标题
DOI：
10.1093/intimm/dxaa038
复制
发表时间：
2020-09-01
影响因子：
4.4
通讯作者：
Takahashi, Yoshimasa
中科院分区：
文献类型：
--
作者：
Tonouchi, Keisuke;Adachi, Yu;Takahashi, Yoshimasa
甲型流感亚型根据血凝素（HA）序列分为1组和2组。由于不同人群中HA的系统发育距离，结合不同人群中多个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抗原免疫可诱导生发中心（GC） B细胞结合1组和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。来自GC B细胞的1556谱系igg能够与感染细胞表面的HA蛋白结合，但不能与天然形式的HA蛋白结合，这表明1S56表位的隐性及其在感染细胞中的暴露。最后，1556谱系IgGs以fc依赖的方式提供对致命感染的保护，独立于病毒中和活性。因此，我们确定1556谱系抗体是实现跨组流感特异性的独特刻板印象。暴露于1S56表位的抗原可能是广泛保护性免疫原的良好候选者。
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.