PI3K induces B-cell development and regulates B cell identity View Full Text


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Article Info

DATE

2018-01-22

AUTHORS

Hend Abdelrasoul, Markus Werner, Corinna S. Setz, Klaus Okkenhaug, Hassan Jumaa

ABSTRACT

Phosphoinositide-3 kinase (PI3K) signaling is important for the survival of numerous cell types and class IA of PI3K is specifically required for the development of B cells but not for T cell development. Here, we show that class IA PI3K-mediated signals induce the expression of the transcription factor Pax5, which plays a central role in B cell commitment and differentiation by activating the expression of central B cell-specific signaling proteins such as SLP-65 and CD19. Defective class IA PI3K function leads to reduction in Pax5 expression and prevents B cell development beyond the stage expressing the precursor B cell receptor (pre-BCR). Investigating the mechanism of PI3K-induced Pax5 expression revealed that it involves a network of transcription factors including FoxO1 and Irf4 that directly binds to the Pax5 gene. Together, our results suggest that PI3K signaling links survival and differentiation of developing B cells with B cell identity and that decreased PI3K activity in pre-B cells results in reduced Pax5 expression and lineage plasticity. More... »

PAGES

1327

References to SciGraph publications

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  • 2002-11-18. The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion in NATURE IMMUNOLOGY
  • 2010-06-13. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates the B cell fate in NATURE IMMUNOLOGY
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  • 2008-05-11. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development in NATURE IMMUNOLOGY
  • 2008-04-30. Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration in NATURE
  • 2008-05-18. SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway in NATURE IMMUNOLOGY
  • 2007-04-17. Pax5: the guardian of B cell identity and function in NATURE IMMUNOLOGY
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-19460-5

    DOI

    http://dx.doi.org/10.1038/s41598-018-19460-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100427017

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29358580


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