Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection
- PMID: 38593796
- PMCID: PMC11096045
- DOI: 10.1016/j.immuni.2024.03.016
Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection
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.
Keywords: B cells; IFN; LCMV; atypical; chronic viral infection; epigenetics; long COVID; memory B cells; scATAC-seq; scRNA-seq.
Copyright © 2024 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
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References
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- Maruyama M, Lam KP, and Rajewsky K (2000). Memory B-cell persistence is independent of persisting immunizing antigen.[see comment][erratum appears in Nature 2001 Jan 18;409(6818):382]. Nature 407, 636–642. - PubMed
-
- Schittek B, and Rajewsky K (1990). Maintenance of B-cell memory by long-lived cells generated from proliferating precursors. Nature 346, 749–751. - PubMed
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