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| Status |
Public on Mar 30, 2021 |
| Title |
Transcription factor Ascl2 promotes geminal center B cell responses through directly regulating AID transcription |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
During germinal center (GC) reactions, activated B cells undergo clonal expansion and functional maturation to produce high-affinity antibodies, and differentiate into plasma and memory cells, accompanied with class-switching recombination (CSR) and somatic hypermutation (SHM). Activation-induced deaminase (AID) is responsible for both CSR and SHM in GC B cells. Transcriptional mechanisms underlying AID regulation and GC B cell reactions are still not well understood. Here, we show that expression of Ascl2 transcription factor is upregulated in GC B cells. Ectopic expression of Ascl2 promotes GC B cell development and enhances antibody production as well as affinity maturation. Conversely, deletion of Ascl2 in B cells impairs the germinal center response. Genome-wide analysis reveals that Ascl2 directly regulates GC B cell-related genes, including AID; ectopic expression of AID in Ascl2-deficient B cells rescues their antibody defects. Thus, Ascl2 regulates AID transcription and promotes germinal center B cell responses.
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| Overall design |
We constructed RVKM-Ascl2 retrovirus, and performed RNA-seq using transfected in vitro cultured activated B cells. Also, ChIP-seq of GC B cells from draining LN of KLH immunized C57BL/6 mice.
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| Contributor(s) |
Sun L, Zhao X, Liu X, Zhong B, Tang H, Jin W, Clevers H, Wang H, Dong C |
| Citation missing |
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| Submission date |
Mar 23, 2021 |
| Last update date |
Apr 02, 2021 |
| Contact name |
Chen Dong |
| Organization name |
Tsinghua University
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| Department |
Institute for Immunology and School of Medicine
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| Lab |
Dongchen's lab
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| Street address |
Haidian District
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| City |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA716539 |
| SRA |
SRP311792 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE169416_RAW.tar |
270.3 Mb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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