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| Status |
Public on Dec 31, 2020 |
| Title |
The DNA methylomes of hyper-IgM syndrome type 2 B cells provide insights into the roles of activation-induced deaminase prior to the germinal center reaction |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Inactivating mutations in activation induced deaminase (AID) lead to hyper-IgM syndrome type 2 (HIGM2), a rare primary antibody deficiency. AID-mediated cytosine deamination has been proposed as mediating active demethylation, although there is evidence both to support and cast doubt on such a role. We here made use of HIGM2 B cells to investigate direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation defects. For genes that undergo demethylation in the transition from naïve to memory B cells but not in HIGM2 individuals, we did not observe AID involvement but a participation of TET enzymes. DNA methylation alterations in HIGM2 naïve B cells are related to premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data supports 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 without involvement of its cytosine deaminase activity.
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| |
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| Overall design |
Tagmentation-based whole-genome bisulfite sequencing of naïve (NBC) and non-class-switched memory B cells (ncsMBC) of two HIGM2 patients and two controls
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| |
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| Contributor(s) |
Català-Moll F, Ballestar E |
| Citation(s) |
33950194 |
| |
| Submission date |
Jul 22, 2019 |
| Last update date |
Jun 03, 2021 |
| Contact name |
Esteban Ballestar |
| Organization name |
Josep Carreras Research Institute (IJC)
|
| Lab |
Epigenetics and Immune Disease
|
| Street address |
Ctra de Can Ruti, Camí de les Escoles s/n
|
| City |
Badalona, Barcelona |
| State/province |
N/A = Not Applicable |
| ZIP/Postal code |
08916 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE172012 |
The DNA methylome and transcriptome of hyper-IgM syndrome type 2 B cells |
|
| Relations |
| BioProject |
PRJNA556010 |
| SRA |
SRP215940 |
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