Galectin-9 binds IgM-BCR to regulate B cell signaling

Anh Cao, Nouf Alluqmani, Fatima Hifza Mohammed Buhari, Laabiah Wasim, Logan K. Smith, Andrew T. Quaile, Michael Shannon, Zaki Hakim, Hossai Furmli, Dylan M. Owen, Alexei Savchenko, Bebhinn Treanor

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19 Citations (Scopus)
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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.
Original languageEnglish
Article number3288
Number of pages18
JournalNature Communications
Volume9
Issue number1
Early online date17 Aug 2018
DOIs
Publication statusPublished - 1 Dec 2018

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