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Kreslavsky, Taras; Vilagos, Bojan; Tagoh, Hiromi; Poliakova, Daniela Kostanova; Schwickert, Tanja A.; Wöhner, Miriam; Jaritz, Markus; Weiss, Siegfried; Taneja, Reshma; Rossner, Moritz J.; Busslinger, Meinrad (2017): Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells. In: Nature Immunology, Vol. 18, No. 4: pp. 442-455
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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.