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

Kreslavsky T, Vilagos B, Tagoh H, Poliakova DK, Schwickert TA, Wöhner M, Jaritz M, Weiss S, Taneja R, Rossner MJ, Busslinger M (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nature Immunology Nature Research

Book Volume: 18

Pages Range: 442-455

Journal Issue: 4

DOI: 10.1038/ni.3694

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 VH 12V κ4 BCR. Expression of a pre-rearranged VH 12V κ4 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.

Authors with CRIS profile

Miriam Wöhner

Involved external institutions

Forschungsinstitut für Molekulare Pathologie / Research Institute of Molecular Pathology (IMP) AT Austria (AT) Vienna Biocenter VBC AT Austria (AT) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) National University of Singapore (NUS) SG Singapore (SG) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Kreslavsky, T., Vilagos, B., Tagoh, H., Poliakova, D.K., Schwickert, T.A., Wöhner, M.,... Busslinger, M. (2017). Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells. Nature Immunology, 18(4), 442-455. https://doi.org/10.1038/ni.3694

MLA:

Kreslavsky, Taras, et al. "Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells." Nature Immunology 18.4 (2017): 442-455.

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