Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection
Date
2024
Authors
Cooper, L.
Xu, H.
Polmear, J.
Kealy, L.
Szeto, C.
Pang, E.S.
Gupta, M.
Kirn, A.
Taylor, J.J.
Jackson, K.J.L.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Immunity, 2024; 57(5):1037-1055.e6
Statement of Responsibility
Lucy Cooper, Hui Xu, Jack Polmear, Liam Kealy, Christopher Szeto, Ee Shan Pang, Mansi Gupta, Alana Kirn, Justin J. Taylor, Katherine J.L. Jackson, Benjamin J. Broomfield, Angela Nguyen, Catarina Gago da Grac, a, Nicole La Gruta, Daniel T. Utzschneider, Joanna R. Groom, Luciano Martelotto, Ian A. Parish, Meredith O, Keeffe, Christopher D. Scharer, Stephanie Gras, and Kim L. Good-Jacobson
Conference Name
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.
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Dissertation Note
Provenance
Description
Published: April 8, 2024
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© 2024 Elsevier Inc. All rights reserved.