First Author | Cao A | Year | 2018 |
Journal | Nat Commun | Volume | 9 |
Issue | 1 | Pages | 3288 |
PubMed ID | 30120235 | Mgi Jnum | J:266494 |
Mgi Id | MGI:6209287 | Doi | 10.1038/s41467-018-05771-8 |
Citation | Cao A, et al. (2018) Galectin-9 binds IgM-BCR to regulate B cell signaling. Nat Commun 9(1):3288 |
abstractText | 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. |