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Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a
J Exp Med. 2015 Apr 6;212(4) :569-80
PMID: 25753579    PMCID: PMC4387290    URL: https://www.ncbi.nlm.nih.gov/pubmed/25753579
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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.
Zhou, Yan Li, Yue-Sheng Bandi, Srinivasa Rao Tang, Lingjuan Shinton, Susan A Hayakawa, Kyoko Hardy, Richard R eng R01AI026782/AI/NIAID NIH HHS/ R01AI49335/AI/NIAID NIH HHS/ P30CA006927/CA/NCI NIH HHS/ R01 AI026782/AI/NIAID NIH HHS/ R01 AI113320/AI/NIAID NIH HHS/ R21 AI117429/AI/NIAID NIH HHS/ R01 AI049335/AI/NIAID NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Exp Med. 2015 Apr 6;212(4):569-80. doi: 10.1084/jem.20141510. Epub 2015 Mar 9.