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Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans
Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leuko...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098069/ https://www.ncbi.nlm.nih.gov/pubmed/30120234 http://dx.doi.org/10.1038/s41467-018-05770-9 |
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author | Giovannone, N. Liang, J. Antonopoulos, A. Geddes Sweeney, J. King, S. L. Pochebit, S. M. Bhattacharyya, N. Lee, G. S. Dell, A. Widlund, H. R. Haslam, S. M. Dimitroff, C. J. |
author_facet | Giovannone, N. Liang, J. Antonopoulos, A. Geddes Sweeney, J. King, S. L. Pochebit, S. M. Bhattacharyya, N. Lee, G. S. Dell, A. Widlund, H. R. Haslam, S. M. Dimitroff, C. J. |
author_sort | Giovannone, N. |
collection | PubMed |
description | Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the β1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers. |
format | Online Article Text |
id | pubmed-6098069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60980692018-08-20 Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans Giovannone, N. Liang, J. Antonopoulos, A. Geddes Sweeney, J. King, S. L. Pochebit, S. M. Bhattacharyya, N. Lee, G. S. Dell, A. Widlund, H. R. Haslam, S. M. Dimitroff, C. J. Nat Commun Article Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the β1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers. Nature Publishing Group UK 2018-08-17 /pmc/articles/PMC6098069/ /pubmed/30120234 http://dx.doi.org/10.1038/s41467-018-05770-9 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 Giovannone, N. Liang, J. Antonopoulos, A. Geddes Sweeney, J. King, S. L. Pochebit, S. M. Bhattacharyya, N. Lee, G. S. Dell, A. Widlund, H. R. Haslam, S. M. Dimitroff, C. J. Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title | Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title_full | Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title_fullStr | Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title_full_unstemmed | Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title_short | Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans |
title_sort | galectin-9 suppresses b cell receptor signaling and is regulated by i-branching of n-glycans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098069/ https://www.ncbi.nlm.nih.gov/pubmed/30120234 http://dx.doi.org/10.1038/s41467-018-05770-9 |
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