title: Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a.
abstract: 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.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Yue-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Srinivasa Rao
authors.initials: SR
authors.lastname: Bandi
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Tang
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Shinton
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111 richard.hardy@fccc.edu.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: C097532:Arid3a protein, mouse; D004268:DNA-Binding Proteins; C570876:Lin28b protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C542687:mirnlet7 microRNA, mouse