Abstract

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.

Details

Title
Galectin-9 binds IgM-BCR to regulate B cell signaling
Author
Cao, Anh 1   VIAFID ORCID Logo  ; Alluqmani, Nouf 2 ; Fatima Hifza Mohammed Buhari 3 ; Laabiah Wasim 1 ; Smith, Logan K 1 ; Quaile, Andrew T 4   VIAFID ORCID Logo  ; Shannon, Michael 5 ; Zaki Hakim 2 ; Hossai Furmli 3 ; Owen, Dylan M 5 ; Savchenko, Alexei 6 ; Treanor, Bebhinn 7   VIAFID ORCID Logo 

1  Department of Immunology, University of Toronto, Toronto, ON, Canada 
2  Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada 
3  Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada 
4  Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada 
5  Department of Physics and Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London Guy’s Campus, London, UK 
6  Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, Health Research Innovation Centre 4AA06, University of Calgary, Calgary, AB, Canada 
7  Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada; Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada 
Pages
1-18
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05771-8
ProQuest document ID
2090573966
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.