| First Author | Kreslavsky T | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 4 | Pages | 442-455 |
| PubMed ID | 28250425 | Mgi Jnum | J:258170 |
| Mgi Id | MGI:6142088 | Doi | 10.1038/ni.3694 |
| Citation | Kreslavsky T, et al. (2017) Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells. Nat Immunol 18(4):442-455 |
| abstractText | 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 VH12Vkappa4 BCR. Expression of a pre-rearranged VH12Vkappa4 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. |
