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| Status |
Public on Sep 22, 2021 |
| Title |
The RNA-binding protein HuR is required for antigen-specific germinal centre B cell selection. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The germinal centre (GC) is a hallmark of adaptive immunity. Gene expression in GCs is tightly regulated but the impact of post-transcriptional mechanisms are largely unknown. Here we show that expression of the RNA binding protein HuR is essential in GCs. In its absence, GC B cells are at a competitive disadvantage and high-affinity antibody production is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively to enable the expression of a Myc- dependent transcriptional program essential for light zone B cells to re-enter into the dark zone for further proliferation and Ig somatic hypermutation. HuR controls the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle. HuR modulates a gene signature associated with DNA deamination preserving GC B cells from extensive DNA damage and cell death.
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| Overall design |
Germinal centre B cells from the dark zone (DZ, CD19+ IgD- CD38- CD95+ CXCR4+ CD86- cells) and the light zone (LZ, CD19+ IgD- CD38- CD95+ CXCR4- CD86+ cells) were sorted (by FACs) from HuRfl/fl (control) or HuRfl/fl AIDCre (HuR KO) mice at day 7 after immunization with NP-KLH in alum.
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| Contributor(s) |
Diaz-Muñoz MD, Osma-Garcia IC, Capitan-Sobrino D, Mouysset M, Bell SE, Lebeurrier M, Turner M |
| Citation(s) |
34772950 |
| Submission date |
Feb 17, 2020 |
| Last update date |
Nov 30, 2021 |
| Contact name |
Manuel D Diaz-Munoz |
| E-mail(s) |
manuel.diaz-munoz@inserm.fr
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| Organization name |
INSERM
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| Department |
UMR1291
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| Lab |
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity)
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| Street address |
CHU Purpan, BP3028
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| City |
Toulouse |
| ZIP/Postal code |
31024 |
| Country |
France |
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| Platforms (2) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA607119 |
| SRA |
SRP249754 |
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