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Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway
Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as prim...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379973/ https://www.ncbi.nlm.nih.gov/pubmed/28341640 http://dx.doi.org/10.1084/jem.20160972 |
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author | Getahun, Andrew Wemlinger, Scott M. Rudra, Pratyaydipta Santiago, Mario L. van Dyk, Linda F. Cambier, John C. |
author_facet | Getahun, Andrew Wemlinger, Scott M. Rudra, Pratyaydipta Santiago, Mario L. van Dyk, Linda F. Cambier, John C. |
author_sort | Getahun, Andrew |
collection | PubMed |
description | Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression. This viral infection-induced PTEN overexpression appears responsible for the suppression of antibody responses observed in infected mice because PTEN deficiency or expression of a constitutively active PI3K rescued function of B cells in infected mice. Conversely, induced overexpression of PTEN in B cells in uninfected mice led to suppression of antibody responses. Finally, we demonstrate that PTEN up-regulation is a common mechanism by which infection induces suppression of antibody responses. Collectively, these findings identify a novel role for PTEN during infection and identify regulation of the PI3K pathway, a mechanism previously shown to silence autoreactive B cells, as a key physiological target to control antibody responses. |
format | Online Article Text |
id | pubmed-5379973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53799732017-10-03 Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway Getahun, Andrew Wemlinger, Scott M. Rudra, Pratyaydipta Santiago, Mario L. van Dyk, Linda F. Cambier, John C. J Exp Med Research Articles Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression. This viral infection-induced PTEN overexpression appears responsible for the suppression of antibody responses observed in infected mice because PTEN deficiency or expression of a constitutively active PI3K rescued function of B cells in infected mice. Conversely, induced overexpression of PTEN in B cells in uninfected mice led to suppression of antibody responses. Finally, we demonstrate that PTEN up-regulation is a common mechanism by which infection induces suppression of antibody responses. Collectively, these findings identify a novel role for PTEN during infection and identify regulation of the PI3K pathway, a mechanism previously shown to silence autoreactive B cells, as a key physiological target to control antibody responses. The Rockefeller University Press 2017-04-03 /pmc/articles/PMC5379973/ /pubmed/28341640 http://dx.doi.org/10.1084/jem.20160972 Text en © 2017 Getahun et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Getahun, Andrew Wemlinger, Scott M. Rudra, Pratyaydipta Santiago, Mario L. van Dyk, Linda F. Cambier, John C. Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title | Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title_full | Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title_fullStr | Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title_full_unstemmed | Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title_short | Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway |
title_sort | impaired b cell function during viral infections due to pten-mediated inhibition of the pi3k pathway |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379973/ https://www.ncbi.nlm.nih.gov/pubmed/28341640 http://dx.doi.org/10.1084/jem.20160972 |
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