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Journal Article

Assembling a gene regulatory network for specification of the B cell fate

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Kieslinger,  Matthias
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grosschedl,  Rudolf
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S1534580704002825?via%3Dihub
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Citation

Medina, K. L., Pongubala, J. M. R., Reddy, K. L., Lancki, D. W., Dekoter, R., Kieslinger, M., et al. (2004). Assembling a gene regulatory network for specification of the B cell fate. Developmental Cell, 7, 607-617. doi:10.1016/j.devcel.2004.08.006.


Cite as: https://hdl.handle.net/21.11116/0000-0007-AC80-6
Abstract
The generation of B lymphocyte precursors is dependent on the combinatorial action of the transcription factors PU.1, Ikaros, E2A, EBF, and Pax-5. Loss of PU.1 results in a severe reduction in Flk2+, IL-7R+ lymphoid progenitors as well as impaired expression of EBF and Pax-5. Restoration of EBF expression facilitates rapid generation of pro-B cells from PU.1−/− progenitors. Molecular analysis suggests that PU.1 directly participates in regulation of the EBF gene. Although PU.1 is dispensable for expression of most early B lineage genes, it is required for CD45R/B220. Using EBF−/− mutant progenitors, we show that EBF induces Pax-5 and the early program of B lineage gene expression. Importantly, Pax-5 does not rescue B cell development from either PU.1−/− or EBF−/− progenitors. Pax-5 expression and function are contingent on EBF. Based on these results, we propose a hierarchical regulatory network for specification and commitment to the B cell fate.