Abstract
Innate-like B-1a cells provide a first line of defense against pathogens, yet little is known about their transcriptional control. Here we identified an essential role for the transcription factor Bhlhe41, with a lesser contribution by Bhlhe40, in controlling B-1a cell differentiation. Bhlhe41(-/-)Bhlhe40(-/-) B-1a cells were present at much lower abundance than were their wild-type counterparts. Mutant B-1a cells exhibited an abnormal cell-surface phenotype and altered B cell receptor (BCR) repertoire exemplified by loss of the phosphatidylcholine-specific V(H)12V kappa 4 BCR. Expression of a pre-rearranged V(H)12V kappa 4 BCR failed to 'rescue' the mutant phenotype and revealed enhanced proliferation accompanied by increased cell death. Bhlhe41 directly repressed the expression of cell-cycle regulators and inhibitors of BCR signaling while enabling pro-survival cytokine signaling. Thus, Bhlhe41 controls the development, BCR repertoire and self-renewal of B-1a cells.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1529-2908 |
Language: | English |
Item ID: | 52727 |
Date Deposited: | 14. Jun 2018, 09:51 |
Last Modified: | 04. Nov 2020, 13:31 |