Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity.
Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity.
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DOI：
10.1016/j.celrep.2022.110482
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发表时间：
2022-03-08
期刊：
影响因子：
8.8
通讯作者：
McGargill, Maureen A.
中科院分区：
文献类型：
--
作者：
Labombarde, Jocelyn G.;Pillai, Meenu R.;Wehenkel, Marie;Lin, Chun-Yang;Keating, Rachael;Brown, Scott A.;Crawford, Jeremy Chase;Brice, David C.;Castellaw, Ashley H.;Mandarano, Alexandra H.;Guy, Clifford S.;Mejia, Juan R.;Lewis, Carlessia D.;Chang, Ti-Cheng;Oshansky, Christine M.;Wong, Sook-San;Webby, Richard J.;Yan, Mei;Li, Quan-Zhen;Marion, Tony N.;Thomas, Paul G.;McGargill, Maureen A.
感染和疫苗接种反复使个体暴露于流感病毒亚型之间保守的抗原。然而，识别可变流感表位的抗体远远多于对保守表位起反应的抗体。阐明导致缺乏广谱反应性流感抗体的因素仍然是开发通用流感疫苗的主要障碍。在这里，我们报告了诱导广泛反应性流感抗体增加了人类和小鼠的自身反应性抗体，并在四种不同的自身免疫性疾病模型中加剧了疾病。重要的是，转移广泛反应的流感抗体会在出现炎症或自身免疫易感性的情况下增加疾病。此外，广泛反应性流感抗体在B细胞耐受性缺陷的小鼠中自发产生。综上所述，这些数据表明，自我耐受机制限制了广泛反应性流感抗体的流行，这种抗体在附加风险因素的背景下可能会加剧疾病。Labombarde等人。研究广谱反应性流感抗体是否有助于自身免疫，这种抗体也可能结合自身抗原。他们证明，这些抗体的诱导也支持在人类和小鼠中发展自身反应性抗体。在炎症或遗传易感性的背景下，转移具有广泛反应性的单抗会加剧自身免疫。
Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors. Labombarde et al. investigate whether broadly reactive influenza antibodies, which may also bind self-antigens, contribute to autoimmunity. They demonstrate that induction of these antibodies also supports development of autoreactive antibodies in both humans and mice. Transferring broadly reactive monoclonal antibodies exacerbates autoimmunity in the context of inflammation or genetic susceptibility.
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