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Sci Rep. 2018 Jan 22;8(1):1327. doi: 10.1038/s41598-018-19460-5.

PI3K induces B-cell development and regulates B cell identity.

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Institute of Immunology, University Medical Center Ulm, 89081, Ulm, Germany.
Molecular Biology department, Genetic Engineering and Biotechnology Division, National Research Centre (NRC), 12622, Giza, Egypt.
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK.
Institute of Immunology, University Medical Center Ulm, 89081, Ulm, Germany.


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.

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