Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis
B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and sur...
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Published in | Cell reports (Cambridge) Vol. 38; no. 7; p. 110386 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.02.2022
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Subjects | |
Online Access | Get full text |
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Summary: | B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.
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•CIC deficiency increases B-1a cell population at the expense of B-2 subsets•The frequency of TrB-1a cells gradually increases in Cic mutant mice with age•CIC deficiency enhances BCR signaling and B-1a cell viability•The CIC-PER2-BHLHE41 axis regulates B-1a cell development and survival
Hong et al. show that CIC is a transcriptional repressor inhibiting B-1a cell formation during postnatal life. CIC levels gradually increase in TrB-1a cells with age, thereby inhibiting B-1a cell differentiation at the adult stage. CIC suppresses BHLHE41, a transcription factor promoting B-1a cell formation, by repressing Per2 expression. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2022.110386 |