PI3K induces B-cell development and regulates B cell identity.
Setz, Corinna S
Nature Publishing Group
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Abdelrasoul, H., Werner, M., Setz, C. S., Okkenhaug, K., & Jumaa, H. (2018). PI3K induces B-cell development and regulates B cell identity.. Scientific reports, 8 (1), 1327. https://doi.org/10.1038/s41598-018-19460-5
Altmetric: 0More detail Article | OPEN PI3K induces B-cell development and regulates B cell identity Hend Abdelrasoul, Markus Werner, Corinna S. Setz, Klaus Okkenhaug & Hassan Jumaa Scientific Reports 8, Article number: 1327 (2018) doi:10.1038/s41598-018-19460-5 Download Citation Adaptive immunityB cells Received: 10 April 2017 Accepted: 02 January 2018 Published online: 22 January 2018 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.
B-Lymphocytes, Cells, Cultured, Cell Line, Animals, Mice, Adaptor Proteins, Signal Transducing, Antigens, CD19, Lymphopoiesis, Cell Lineage, Interferon Regulatory Factors, Phosphatidylinositol 3-Kinases, PAX5 Transcription Factor, Forkhead Box Protein O1
External DOI: https://doi.org/10.1038/s41598-018-19460-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/274601
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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