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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-...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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.
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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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