Galectin-9 binds IgM-BCR to regulate B cell signaling
Autor: | Alexei Savchenko, Fatima Hifza Mohammed Buhari, Andrew T. Quaile, Nouf Alluqmani, Zaki Hakim, Logan K. Smith, Michael Shannon, Hossai Furmli, Bebhinn Treanor, Laabiah Wasim, Anh Cao, Dylan M. Owen |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
animal structures Galectins Sialic Acid Binding Ig-like Lectin 2 Science B-cell receptor Receptors Antigen B-Cell General Physics and Astronomy Models Biological Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Membrane Microdomains 0302 clinical medicine hemic and lymphatic diseases medicine otorhinolaryngologic diseases Animals lcsh:Science Receptor Cells Cultured B cell Galectin B-Lymphocytes Multidisciplinary Chemistry CD22 breakpoint cluster region General Chemistry Acquired immune system 3. Good health Cell biology Mice Inbred C57BL stomatognathic diseases Immobilized Proteins 030104 developmental biology medicine.anatomical_structure Immunoglobulin M Leukocyte Common Antigens lcsh:Q Signal transduction 030217 neurology & neurosurgery Protein Binding Signal Transduction |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-18 (2018) Cao, A, Alluqmani, N, Buhari, F H M, Wasim, L, Smith, L K, Quaile, A T, Shannon, M, Hakim, Z, Furmli, H, Owen, D M, Savchenko, A & Treanor, B 2018, ' Galectin-9 binds IgM-BCR to regulate B cell signaling ', Nature Communications, vol. 9, no. 1, 3288 . https://doi.org/10.1038/s41467-018-05771-8 Nature Communications |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-018-05771-8 |
Popis: | 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. The galectin family of secreted lectins are important regulators of immune cell function; however, their role in B cell responses is poorly understood. Here, the authors identify IgM-BCR as a ligand for galectin-9. In resting naive cells, they show that galectin-9 mediates a close association between IgM and CD22. |
Databáze: | OpenAIRE |
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