Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses.
Authors
Arutyunyan, Anna
Bonder, Marc Jan
de la Calle-Fabregat, Carlos
Garcia-Alonso, Luz
Handfield, Louis-François
Ciudad, Laura
Català-Moll, Francesc
Rodríguez-Cortez, Virginia C
Polanski, Krzysztof
Mamanova, Lira
van Dongen, Stijn
Kiselev, Vladimir Yu
Martín, Javier
López-Granados, Eduardo
Publication Date
2022-04-01Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Rodríguez-Ubreva, J., Arutyunyan, A., Bonder, M. J., Del Pino-Molina, L., Clark, S. J., de la Calle-Fabregat, C., Garcia-Alonso, L., et al. (2022). Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-29450-x
Description
Funder: Wellcome Trust
Abstract
Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.
Keywords
Germinal Center, B-Lymphocytes, Humans, Common Variable Immunodeficiency, Epigenesis, Genetic, Epigenomics
Identifiers
35365635, PMC8975885
External DOI: https://doi.org/10.1038/s41467-022-29450-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336707
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