ArticleNucleic acids research2021
Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Germinal Center Selection and Plasma Cell Differentiation.Immunological reviews · 2026Review
- AID and TET2 cooperate to demethylate Irf4 for plasma cell fate in germinal center B cells.The Journal of experimental medicine · 2026Article
- ICF syndrome: An epigenetic paradigm for primary immunodeficiencies.Journal of human immunity · 2026Review
- Review
- Epigenetic regulation of B cells and its role in autoimmune pathogenesis.Cellular & molecular immunology · 2022Review
- DNA Methylation and Immune Memory Response.Cells · 2021Review
- Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease.Genes · 2020Review
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which ∼25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis indicates that AID is not directly involved. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns.
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