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PI3K induces B-cell development and regulates B cell identity
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 fa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778048/ https://www.ncbi.nlm.nih.gov/pubmed/29358580 http://dx.doi.org/10.1038/s41598-018-19460-5 |
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author | Abdelrasoul, Hend Werner, Markus Setz, Corinna S. Okkenhaug, Klaus Jumaa, Hassan |
author_facet | Abdelrasoul, Hend Werner, Markus Setz, Corinna S. Okkenhaug, Klaus Jumaa, Hassan |
author_sort | Abdelrasoul, Hend |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5778048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57780482018-01-31 PI3K induces B-cell development and regulates B cell identity Abdelrasoul, Hend Werner, Markus Setz, Corinna S. Okkenhaug, Klaus Jumaa, Hassan Sci Rep Article 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. Nature Publishing Group UK 2018-01-22 /pmc/articles/PMC5778048/ /pubmed/29358580 http://dx.doi.org/10.1038/s41598-018-19460-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Abdelrasoul, Hend Werner, Markus Setz, Corinna S. Okkenhaug, Klaus Jumaa, Hassan PI3K induces B-cell development and regulates B cell identity |
title | PI3K induces B-cell development and regulates B cell identity |
title_full | PI3K induces B-cell development and regulates B cell identity |
title_fullStr | PI3K induces B-cell development and regulates B cell identity |
title_full_unstemmed | PI3K induces B-cell development and regulates B cell identity |
title_short | PI3K induces B-cell development and regulates B cell identity |
title_sort | pi3k induces b-cell development and regulates b cell identity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778048/ https://www.ncbi.nlm.nih.gov/pubmed/29358580 http://dx.doi.org/10.1038/s41598-018-19460-5 |
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