Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a
| Autor: | Srinivasa Rao Bandi, Susan A. Shinton, Richard R. Hardy, Lingjuan Tang, Yue-Sheng Li, Yan Zhou, Kyoko Hayakawa |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Immunology
B-Lymphocyte Subsets Mice SCID Biology Article 03 medical and health sciences Mice 0302 clinical medicine Fetus Transduction Genetic medicine Immunology and Allergy Animals Lymphopoiesis Progenitor cell Transcription factor B cell 030304 developmental biology Regulation of gene expression 0303 health sciences Mice Inbred BALB C Precursor Cells B-Lymphoid breakpoint cluster region RNA-Binding Proteins Cell biology DNA-Binding Proteins MicroRNAs medicine.anatomical_structure Gene Expression Regulation Ectopic expression Female Bone marrow 030215 immunology Transcription Factors |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Zhou et al. demonstrate a requirement for the Let-7–Lin28b axis regulating a shift in development between fetal liver and bone marrow B lymphocyte progenitors in the generation of B1 versus B2 B cells. Specifically, the transcription factor Arid3a, induced by Lin28b and a target of Let-7 miRNA, is sufficient to recapitulate fetal B cell development from bone marrow progenitors. 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. |
| Databáze: | OpenAIRE |
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