Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313405955> ?p ?o ?g. }
Showing items 1 to 64 of
64
with 100 items per page.
- W4313405955 endingPage "112.05" @default.
- W4313405955 startingPage "112.05" @default.
- W4313405955 abstract "Abstract The production of antibody and formation of immunological memory underpins vaccine success. Yet, chronic viral infections result in an inadequate humoral response, and little is known about the mechanisms underpinning this dysregulation. We therefore utilised acute or chronic strains of lymphocytic choriomeningitis virus (LCMV) to investigate B cell behaviour in vivo during chronic infection. Our work revealed that chronic infection altered epigenetic regulation of B cell fate, and a key epigenetic target could be therapeutically modulated to correct antibody responses. Deep-sequencing revealed key differences in chromatin accessibility of B cells responding to acute vs chronic infection, leading us to investigate the Polycomb repressive complex 1 component BMI-1. BMI-1 was upregulated in germinal centre B cells of mice infected with chronic LCMV, compared to acute LCMV. B cell-intrinsic deletion of BMI-1 resulted in a restoration of splenic architecture, and an enhanced and rapid ability to clear virus. Deletion of BMI-1 re-established appropriate c-Myc expression in B cells, concomitant with improved quality of antibody with enhanced antibody-dependent effector function and increased neutralising capacity. Together, our data defines BMI-1 as a crucial immune modifier that controls antibody-mediated responses in chronic infection. Further, single-cell RNA-seq and genetic models revealed that excess immune complexes, in concert with dysregulated complement-mediated functions, contribute to ineffective memory formation during chronic viral infection. Understanding the molecular events that may sustain dysfunction lays the foundation for improving therapeutic interventions in chronic infectious diseases. Supported by Bellberry-Viertel Senior Medical Research Fellowship and an AAI Careers in Immunology Fellowship." @default.
- W4313405955 created "2023-01-06" @default.
- W4313405955 creator A5031311509 @default.
- W4313405955 creator A5039375349 @default.
- W4313405955 creator A5084839423 @default.
- W4313405955 date "2022-05-01" @default.
- W4313405955 modified "2023-10-16" @default.
- W4313405955 title "Targeting intrinsic regulators of antibody and B cell memory to control chronic viral infection" @default.
- W4313405955 doi "https://doi.org/10.4049/jimmunol.208.supp.112.05" @default.
- W4313405955 hasPublicationYear "2022" @default.
- W4313405955 type Work @default.
- W4313405955 citedByCount "0" @default.
- W4313405955 crossrefType "journal-article" @default.
- W4313405955 hasAuthorship W4313405955A5031311509 @default.
- W4313405955 hasAuthorship W4313405955A5039375349 @default.
- W4313405955 hasAuthorship W4313405955A5084839423 @default.
- W4313405955 hasConcept C104317684 @default.
- W4313405955 hasConcept C159047783 @default.
- W4313405955 hasConcept C159654299 @default.
- W4313405955 hasConcept C167672396 @default.
- W4313405955 hasConcept C203014093 @default.
- W4313405955 hasConcept C2778453870 @default.
- W4313405955 hasConcept C2779359726 @default.
- W4313405955 hasConcept C2780190958 @default.
- W4313405955 hasConcept C3019392825 @default.
- W4313405955 hasConcept C41091548 @default.
- W4313405955 hasConcept C54355233 @default.
- W4313405955 hasConcept C86803240 @default.
- W4313405955 hasConcept C8891405 @default.
- W4313405955 hasConcept C96926380 @default.
- W4313405955 hasConceptScore W4313405955C104317684 @default.
- W4313405955 hasConceptScore W4313405955C159047783 @default.
- W4313405955 hasConceptScore W4313405955C159654299 @default.
- W4313405955 hasConceptScore W4313405955C167672396 @default.
- W4313405955 hasConceptScore W4313405955C203014093 @default.
- W4313405955 hasConceptScore W4313405955C2778453870 @default.
- W4313405955 hasConceptScore W4313405955C2779359726 @default.
- W4313405955 hasConceptScore W4313405955C2780190958 @default.
- W4313405955 hasConceptScore W4313405955C3019392825 @default.
- W4313405955 hasConceptScore W4313405955C41091548 @default.
- W4313405955 hasConceptScore W4313405955C54355233 @default.
- W4313405955 hasConceptScore W4313405955C86803240 @default.
- W4313405955 hasConceptScore W4313405955C8891405 @default.
- W4313405955 hasConceptScore W4313405955C96926380 @default.
- W4313405955 hasIssue "1_Supplement" @default.
- W4313405955 hasLocation W43134059551 @default.
- W4313405955 hasOpenAccess W4313405955 @default.
- W4313405955 hasPrimaryLocation W43134059551 @default.
- W4313405955 hasRelatedWork W1969362413 @default.
- W4313405955 hasRelatedWork W2791325112 @default.
- W4313405955 hasRelatedWork W2908094543 @default.
- W4313405955 hasRelatedWork W3172566042 @default.
- W4313405955 hasRelatedWork W3215527916 @default.
- W4313405955 hasRelatedWork W4200628384 @default.
- W4313405955 hasRelatedWork W4311129803 @default.
- W4313405955 hasRelatedWork W4313374641 @default.
- W4313405955 hasRelatedWork W4313405955 @default.
- W4313405955 hasRelatedWork W4327857457 @default.
- W4313405955 hasVolume "208" @default.
- W4313405955 isParatext "false" @default.
- W4313405955 isRetracted "false" @default.
- W4313405955 workType "article" @default.