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| Status |
Public on Sep 21, 2017 |
| Title |
Bach2 promotes B cell receptor-induced proliferation of B lymphocytes and represses cyclin-dependent kinase inhibitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Bach2 (BTB and CNC homology-2) is a transcriptional repressor which is required for the formation of the germinal center (GC) and reactions including class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in B cells within the GC. While BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling. Following BCR engagement in vitro, B cells from Bach2-deficient (Bach2-/-) mice showed lower incorporation of 5-bromo-2'-deoxyuridine (BrdU) and reduced cell cycle progression compared with wild-type (WT) cells. Bach2-/- B cells also underwent increased apoptosis as evidenced by an elevated frequency of sub-G1 cells and early apoptotic cells. Transcriptome analysis of BCR-engaged B cells from Bach2-/- mice revealed reduced expression of the anti-apoptotic gene Bcl2l1 encoding Bcl-XL, and an elevated expression of cyclin-dependent kinase inhibitor (CKI) family genes including Cdkn1a, Cdkn2a and Cdkn2b. Reconstitution of Bcl-XL expression partially rescued the proliferation defect of Bach2-/- B cells. Chromatin imunoprecipitation (ChIP) experiments showed that Bach2 bound to the CKI family genes, indicating that these genes are direct repression targets of Bach2. These findings identify Bach2 as a requisite factor for sustaining high levels of BCR-induced proliferation, survival and cell cycle progression, and promotes expression of Bcl-XL and repression of CKI genes, respectively. BCR-induced proliferation defects may contribute to impaired GC formation observed in Bach2-/- mice.
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| Overall design |
In order to reveal the molecular mechanism of prolifrerative difects of Bach2-/- follicular zone B cells in response to B cell receptor signaling, gene expression profiles of Bach2-/- follicular zone B cells were compared to its of wild-type follicular zone B cells before and after B cell receptor stimulation.
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| Contributor(s) |
Miura Y, Muto A, Matsumoto M, Igarashi K |
| Citation missing |
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| |
| Submission date |
Sep 19, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Akihiko Muto |
| E-mail(s) |
mutoa@med.tohoku.ac.jp
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| Phone |
+81-22-717-7597
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| Organization name |
Tohoku University Graduate School of Medicine
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| Department |
Biochemistry
|
| Street address |
Seiryou-machi 2-1
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| City |
Sendai |
| State/province |
Miyagi |
| ZIP/Postal code |
980-8575 |
| Country |
Japan |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA408059 |
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