Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections
CELL, cilt.189, sa.11, ss.3236-3276, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 189 Sayı: 11
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.cell.2026.04.013
- Dergi Adı: CELL
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO)
- Sayfa Sayıları: ss.3236-3276
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
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.