Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
J Infect Dis. 2017 Dec 27;217(1):3-11. doi: 10.1093/infdis/jix546.
Influenza A virus (IAV) and influenza B virus (IBV) cause substantial morbidity and mortality during annual epidemics. Two distinct lineages of IBV are distinguished, based on variation in hemagglutinin (HA): B/Victoria/2/87-like (B/Vic) and B/Yamagata/16/88-like (B/Yam). Here, we show that, in humans, primary IBV infection with either lineage induces HA-specific antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. IBV infection induced antibodies specific to the HA head and stalk, but only HA stalk-specific antibodies mediated ADCC efficiently and displayed cross-reactivity with IBV of both lineages. This corresponds to recent findings that 2 points of contact between the effector and target cell (ie, HA and sialic acid, respectively, and the fragment crystallizable [Fc] domain and Fcγ receptor IIIα, respectively) are required for efficient ADCC activity and that antibodies specific for the receptor-binding site located in the head domain of HA therefore fail to mediate ADCC. Potentially, ADCC-mediating antibodies directed to the HA stalk of IBV contribute to cross-protective immunity to IBV of both lineages.
甲型流感病毒（IAV）和乙型流感病毒（IBV）在每年的流行中会导致大量的发病率和死亡率。根据血凝素（HA）的变异，将 IBV 分为两个不同的谱系：B/Victoria/2/87 样（B/Vic）和 B/Yamagata/16/88 样（B/Yam）。在这里，我们表明，在人类中，与任何一个谱系的原发性 IBV 感染都会诱导产生针对 HA 的抗体依赖的细胞毒性（ADCC）介导的抗体。IBV 感染诱导针对 HA 头部和茎部的特异性抗体，但只有 HA 茎部特异性抗体能够有效地介导 ADCC，并与两个谱系的 IBV 发生交叉反应。这与最近的研究结果一致，即效应细胞和靶细胞之间的 2 个接触点（即 HA 和唾液酸，以及片段结晶（Fc）结构域和 Fcγ受体 IIIα）对于有效的 ADCC 活性是必需的，而位于 HA 头部结构域的受体结合位点的特异性抗体因此不能介导 ADCC。潜在地，针对 IBV 的 HA 茎部的 ADCC 介导抗体有助于对两种谱系的 IBV 的交叉保护免疫。
