巴黎大学Pascal Chappert团队的最新研究提出了亲和成熟的B细胞反应中和I型干扰素是严重病毒感染的基础。2026年5月6日出版的《细胞》杂志发表了这项成果。
该团队报道，AAN-I-IFNs+阳性的COVID-19肺炎患者体内循环的i型ifn特异性B细胞与遗传来源的T细胞耐受性缺陷患者难以区分。这种自身免疫反应动员高度多样化和稳定的循环B细胞反应，在严重病毒感染之前被检测到，并通过扩展的体细胞超突变获得对I型IFNs的高亲和力和中和潜力。X射线晶体学和对数百种患者来源的单克隆抗体的AlphaFold3结构分析揭示了这种反应的扩展广度，靶向覆盖I型IFNs所有方面的三个主要B细胞表位。这些发现支持了一种模型，即生发中心衍生的针对i型IFNs的记忆性B细胞反应在严重病毒感染之前就已经建立起来，从而提供了一种将T细胞耐受缺陷与严重病毒疾病背后的致病性AAN-I-IFNs联系起来的核心机制。
据悉，中和I型干扰素的自身抗体（AAN-I-IFNs）成为越来越多的严重病毒性疾病的全球、常见和强有力的决定因素。
附：英文原文
Title: Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections
Author: Morgane Fournier, Matthias Vanderkerken, Karim Dorgham, Paul Bastard, Olivia Ahouzi, Stephane Duquerroy, Ngoc Khanh Nguyen, Manon Broutin, Manon Charlet, Alexis Vandenberghe, Paolo Van Endert, Lucy Bizien, Omaira Da Mata-Jardin, Andrés Ferrio-Iriarte, Ahmed Haouz, Thibaut Belmondo, Sophie Hüe, Alessandro Borghesi, Carlos Rodríguez-Gallego, Donald C. Vinh, Evangelos Andreakos, Filomeen Haerynck, Rabih Halwani, Qiang Pan-Hammarstrm, Niklas K. Bjrkstrm, Benedikt Strunz, Trine H. Mogensen, Antonio Piralla, Stefania Varchetta, Jorge Freixinet, Lucie Roussel, Sophie Trouillet Assant, Bénédicte Neven, Romain Levy, Tom le Voyer, Ottavia M. Delmonte, Cliona O’Farrelly, Jacques Rivière, Blanca Amador Borrero, Amélie Servettaz, Roger D. Kouyos, Daniel E. Kaufmann, Etienne Crickx, Marc Michel, Anne Puel, Laurent Abel, Charles-Edouard Luyt, Alexis Mathian, Kai Kisand, Darragh Duffy, Lluis Quintana-Murci, Zahir Amoura, Benjamin G. Hale, Jean-Claude Weill, Jean-Laurent Casanova, Felix A. Rey, Guy Gorochov, Pascal Chappert
Issue&Volume: 2026-05-06
Abstract: Autoantibodies neutralizing type-I interferons (AAN-I-IFNs) emerge as global, common, and strong determinants of a growing number of severe viral diseases. We report that AAN-I-IFNs+ patients with life-threatening COVID-19 pneumonia harbor circulating type-I IFN-specific B cells indistinguishable from patients bearing T cell tolerance defects of genetic origin. This autoimmune response mobilizes a highly diverse and stable circulating B cell response that is detected prior to severe viral infection and acquires high affinity and neutralization potential to type-I IFNs through extended somatic hypermutation. X-ray crystallography and AlphaFold3 structural analysis of hundreds of patient-derived monoclonal antibodies reveals the extended breadth of this response, targeting three major B cell epitopes covering all facets of type-I IFNs. These findings support a model in which a germinal-center-derived memory B cell response directed against type-I IFNs is established before severe viral infection, providing a core mechanism linking T cell tolerance defect to pathogenic AAN-I-IFNs underlying severe viral diseases.
DOI: 10.1016/j.cell.2026.04.013
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00438-1