| First Author | Zhou Y | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 4 | Pages | 569-80 |
| PubMed ID | 25753579 | Mgi Jnum | J:222093 |
| Mgi Id | MGI:5643965 | Doi | 10.1084/jem.20141510 |
| Citation | Zhou Y, et al. (2015) Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a. J Exp Med 212(4):569-80 |
| abstractText | Mouse B cell precursors from fetal liver and adult bone marrow (BM) generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal "B-1" and adult "B-2." Recently, Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of B cell antigen receptor (BCR) signaling in this process was addressed. Here, we report key advances in our understanding of the regulation of B-1/B-2 development. First, modulation of Let-7 in fetal pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for the generation of B1a B cells from Lin28b-transduced BM progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertoire of Lin28b-induced BM B1a B cells differs from that of normal B1a, suggesting persisting differences from fetal progenitors. Finally, we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult pro-B cells and whose silencing by knockdown blocks B-1 development in fetal pro-B cells. |
