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del Pino-MolinaL.pdf (3.19 MB)

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2019-04-24

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cc by (c) Pino Molina et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171562

Impaired CpG Demethylation in Common Variable Immunodeficiency Associates With B Cell Phenotype and Proliferation Rate

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Recurs relacionat

https://doi.org/10.3389/fimmu.2019.00878

Resum

Common Variable Immunodeficiency (CVID) is characterized by impaired antibody production and poor terminal differentiation of the B cell compartment, yet its pathogenesis is still poorly understood. We first reported the occurrence of epigenetic alterations in CVID by high-throughput methylation analysis in CVID-discordant monozygotic twins. Data from a recent whole DNA methylome analysis throughout different stages of normal B cell differentiation allowed us to design a new experimental approach. We selected CpG sites for analysis based on two criteria: one, CpGs with potential association with the transcriptional status of relevant genes for B cell activation and differentiation; and two, CpGs that undergo significant demethylation from naive to memory B cells in healthy individuals. DNA methylation was analyzed by bisulfite pyrosequencing of specific CpG sites in sorted naive and memory B cell subsets from CVID patients and healthy donors. We observed impaired demethylation in two thirds of the selected CpGs in CVID memory B cells, in genes that govern B cell-specific processes or participate in B cell signaling. The degree of demethylation impairment associated with the extent of the memory B cell reduction. The impaired demethylation in such functionally relevant genes as AICDA in switched memory B cells correlated with a lower proliferative rate. Our new results reinforce the hypothesis of altered demethylation during B cell differentiation as a contributing pathogenic mechanism to the impairment of B cell function and maturation in CVID. In particular, deregulated epigenetic control of AICDA could play a role in the defective establishment of a post-germinal center B cell compartment in CVID.

Matèries

Malalties immunològiques, Cèl·lules B

Matèries (anglès)

Immunologic diseases, B cells

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

PINO MOLINA, Lucía del, et al. Impaired CpG Demethylation in Common Variable Immunodeficiency Associates With B Cell Phenotype and Proliferation Rate. Frontiers in Immunology. 2019. Vol. 10. [consulted: 21 of August of 2026]. Available at: https://hdl.handle.net/2445/171562

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