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Galectin-9 binds IgM-BCR to regulate B cell signaling
The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-...
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/PMC6098130/ https://www.ncbi.nlm.nih.gov/pubmed/30120235 http://dx.doi.org/10.1038/s41467-018-05771-8 |
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author | Cao, Anh Alluqmani, Nouf Buhari, Fatima Hifza Mohammed Wasim, Laabiah Smith, Logan K. Quaile, Andrew T. Shannon, Michael Hakim, Zaki Furmli, Hossai Owen, Dylan M. Savchenko, Alexei Treanor, Bebhinn |
author_facet | Cao, Anh Alluqmani, Nouf Buhari, Fatima Hifza Mohammed Wasim, Laabiah Smith, Logan K. Quaile, Andrew T. Shannon, Michael Hakim, Zaki Furmli, Hossai Owen, Dylan M. Savchenko, Alexei Treanor, Bebhinn |
author_sort | Cao, Anh |
collection | PubMed |
description | The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-9-deficient B cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely abolishes BCR signaling. We investigated the molecular mechanism for galectin-9-mediated inhibition of BCR signaling using super-resolution imaging and single-particle tracking. We show that galectin-9 merges pre-existing nanoclusters of IgM-BCR, immobilizes IgM-BCR, and relocalizes IgM-BCR together with the inhibitory molecules CD45 and CD22. In resting naive cells, we use dual-color super-resolution imaging to demonstrate that galectin-9 mediates the close association of IgM and CD22, and propose that the loss of this association provides a mechanism for enhanced activation of galectin-9-deficient B cells. |
format | Online Article Text |
id | pubmed-6098130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60981302018-08-20 Galectin-9 binds IgM-BCR to regulate B cell signaling Cao, Anh Alluqmani, Nouf Buhari, Fatima Hifza Mohammed Wasim, Laabiah Smith, Logan K. Quaile, Andrew T. Shannon, Michael Hakim, Zaki Furmli, Hossai Owen, Dylan M. Savchenko, Alexei Treanor, Bebhinn Nat Commun Article The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-9-deficient B cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely abolishes BCR signaling. We investigated the molecular mechanism for galectin-9-mediated inhibition of BCR signaling using super-resolution imaging and single-particle tracking. We show that galectin-9 merges pre-existing nanoclusters of IgM-BCR, immobilizes IgM-BCR, and relocalizes IgM-BCR together with the inhibitory molecules CD45 and CD22. In resting naive cells, we use dual-color super-resolution imaging to demonstrate that galectin-9 mediates the close association of IgM and CD22, and propose that the loss of this association provides a mechanism for enhanced activation of galectin-9-deficient B cells. Nature Publishing Group UK 2018-08-17 /pmc/articles/PMC6098130/ /pubmed/30120235 http://dx.doi.org/10.1038/s41467-018-05771-8 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 Cao, Anh Alluqmani, Nouf Buhari, Fatima Hifza Mohammed Wasim, Laabiah Smith, Logan K. Quaile, Andrew T. Shannon, Michael Hakim, Zaki Furmli, Hossai Owen, Dylan M. Savchenko, Alexei Treanor, Bebhinn Galectin-9 binds IgM-BCR to regulate B cell signaling |
title | Galectin-9 binds IgM-BCR to regulate B cell signaling |
title_full | Galectin-9 binds IgM-BCR to regulate B cell signaling |
title_fullStr | Galectin-9 binds IgM-BCR to regulate B cell signaling |
title_full_unstemmed | Galectin-9 binds IgM-BCR to regulate B cell signaling |
title_short | Galectin-9 binds IgM-BCR to regulate B cell signaling |
title_sort | galectin-9 binds igm-bcr to regulate b cell signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098130/ https://www.ncbi.nlm.nih.gov/pubmed/30120235 http://dx.doi.org/10.1038/s41467-018-05771-8 |
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