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DOI 10.1016/j.cell.2026.04.013

Медицинская библиотека · Cell · 2026

Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.

Fournier Morgane, Vanderkerken Matthias, Dorgham Karim, Bastard Paul, Ahouzi Olivia, Duquerroy Stephane, Nguyen Ngoc Khanh, Broutin Manon, Charlet Manon, Vandenberghe Alexis, Van Endert Paolo, Bizien Lucy, Da Mata-Jardin Omaira, Ferriño-Iriarte Andrés, Haouz Ahmed, Belmondo Thibaut, Hüe Sophie, Borghesi Alessandro, Rodríguez-Gallego Carlos, Vinh Donald C, Andreakos Evangelos, Haerynck Filomeen, Halwani Rabih, Pan-Hammarström Qiang, Björkström Niklas K, Strunz Benedikt, Mogensen Trine H, COVID Human Genetic Effort, Piralla Antonio, Varchetta Stefania, Freixinet Jorge, Roussel Lucie, Trouillet Assant Sophie, Neven Bénédicte, Levy Romain, le Voyer Tom, Delmonte Ottavia M, O'Farrelly Cliona, Rivière Jacques, Amador Borrero Blanca, Servettaz Amélie, Kouyos Roger D, Kaufmann Daniel E, Crickx Etienne, Michel Marc, Puel Anne, Abel Laurent, Luyt Charles-Edouard, Mathian Alexis, Kisand Kai, Duffy Darragh, Quintana-Murci Lluis, Amoura Zahir, Hale Benjamin G, Weill Jean-Claude, Casanova Jean-Laurent, Rey Felix A, Gorochov Guy, Chappert Pascal, Mahévas Matthieu

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Аннотация

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.

Для цитирования: Fournier Morgane, Vanderkerken Matthias, Dorgham Karim, Bastard Paul, Ahouzi Olivia, Duquerroy Stephane, Nguyen Ngoc Khanh, Broutin Manon, Charlet Manon, Vandenberghe Alexis, Van Endert Paolo, Bizien Lucy, Da Mata-Jardin Omaira, Ferriño-Iriarte Andrés, Haouz Ahmed, Belmondo Thibaut, Hüe Sophie, Borghesi Alessandro, Rodríguez-Gallego Carlos, Vinh Donald C, Andreakos Evangelos, Haerynck Filomeen, Halwani Rabih, Pan-Hammarström Qiang, Björkström Niklas K, Strunz Benedikt, Mogensen Trine H, COVID Human Genetic Effort, Piralla Antonio, Varchetta Stefania, Freixinet Jorge, Roussel Lucie, Trouillet Assant Sophie, Neven Bénédicte, Levy Romain, le Voyer Tom, Delmonte Ottavia M, O'Farrelly Cliona, Rivière Jacques, Amador Borrero Blanca, Servettaz Amélie, Kouyos Roger D, Kaufmann Daniel E, Crickx Etienne, Michel Marc, Puel Anne, Abel Laurent, Luyt Charles-Edouard, Mathian Alexis, Kisand Kai, Duffy Darragh, Quintana-Murci Lluis, Amoura Zahir, Hale Benjamin G, Weill Jean-Claude, Casanova Jean-Laurent, Rey Felix A, Gorochov Guy, Chappert Pascal, Mahévas Matthieu. Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.. Cell. 2026. DOI: 10.1016/j.cell.2026.04.013.

Предметные рубрики MeSH

HumansInterferon Type ICOVID-19B-LymphocytesSARS-CoV-2Antibodies, NeutralizingCrystallography, X-RayEpitopes, B-LymphocyteAutoantibodies
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