Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a [miRNA]

ABSTRACT: Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal M-bM-^@M-^\B-1M-bM-^@M-^] and adult M-bM-^@M-^\B-2M-bM-^@M-^]. 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 BCR signaling in this process was addressed. Here we report important 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 generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. 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 knockdown blocks B-1 development in fetal Pro-B cells. 3 individual sorts of Fr.B/C fractions from bone marrow and fetal liver of BALB/c mice

ORGANISM(S): Mus musculus

SUBMITTER: Richard Hardy 

PROVIDER: E-GEOD-65535 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress