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Essential role of the transcription factor Bhlhe41 in regulating the self-renewal and BCR repertoire of B-1a cells

ABSTRACT: The innate-like B-1a cells provide a first line of defense against pathogens, and yet little is known about their transcriptional control. Here we identified an essential role of the transcription factor Bhlhe41, with a lesser contribution of Bhlhe40, in controlling late stages of B-1a cell differentiation. Bhlhe41/Bhlhe40 mutant B-1a cells were strongly reduced and had an abnormal cell-surface phenotype and altered B-cell receptor (BCR) repertoire, as exemplified by loss of the phosphatidylcholine-specific Vh12/Vk4 BCR. Expression of a pre-rearranged Vh12/Vk4 BCR failed to rescue the mutant phenotype and revealed enhanced proliferation accompanied with increased cell death, implicating Bhlhe41 in controlling the self-renewal of B-1a cells. Bhlhe41 directly repressed the expression of cell cycle regulators and inhibitors of BCR signaling, while activating pro-survival cytokine signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE93764 | GEO | 2017/01/19

SECONDARY ACCESSION(S): PRJNA362312

REPOSITORIES: GEO

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