Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection

Cooper, L; Xu, H; Polmear, J; Kealy, L; Szeto, C; Pang, ES; Gupta, M; Kirn, A; Taylor, JJ; Jackson, KJL; Broomfield, BJ; Nguyen, A; Gago da Gra&#231;a, C; La Gruta, N; Utzschneider, DT; Groom, JR; Martelotto, L; Parish, IA; O&#39;Keeffe, M; Scharer, CD; Gras, S; Good-Jacobson, KL

Author(s): Cooper, L; Xu, H; Polmear, J; Kealy, L; Szeto, C; Pang, ES; Gupta, M; Kirn, A; Taylor, JJ; Jackson, KJL; Broomfield, BJ; Nguyen, A; Gago da Graça, C; La Gruta, N; Utzschneider, DT; Groom, JR; Martelotto, L; Parish, IA; O'Keeffe, M; Scharer, CD; Gras, S; Good-Jacobson, KL;
Details: Publication Year 2024-05-14,Volume 57,Issue #5,Page 1037-1055.e6
Journal Title: Immunity
Publication Type: Research article
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.
Publisher: Cell Press
Keywords: Animals; *Interferon Type I/metabolism/immunology; *Lymphocytic Choriomeningitis/immunology/virology; Mice; *Lymphocytic choriomeningitis virus/immunology; *Memory B Cells/immunology; *Epigenesis, Genetic; Mice, Inbred C57BL; Receptor, Interferon alpha-beta/genetics; Immunologic Memory/immunology; Chronic Disease; B-Lymphocyte Subsets/immunology; Single-Cell Analysis; B cells; Ifn; Lcmv; atypical; chronic viral infection; epigenetics; long COVID; memory B cells; scATAC-seq; scRNA-seq
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.immuni.2024.03.016
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-04 04:37:32

Last Modified: 2024-07-04 04:49:35