Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.
Immunity
; 57(5): 1037-1055.e6, 2024 May 14.
Article
en En
| MEDLINE
| ID: mdl-38593796
ABSTRACT
Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
Epigénesis Genética
/
Células B de Memoria
/
Coriomeningitis Linfocítica
/
Virus de la Coriomeningitis Linfocítica
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia