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

Author

Listed:
  • Anh Cao

    (University of Toronto)

  • Nouf Alluqmani

    (University of Toronto)

  • Fatima Hifza Mohammed Buhari

    (University of Toronto Scarborough)

  • Laabiah Wasim

    (University of Toronto)

  • Logan K. Smith

    (University of Toronto)

  • Andrew T. Quaile

    (University of Toronto)

  • Michael Shannon

    (King’s College London Guy’s Campus)

  • Zaki Hakim

    (University of Toronto)

  • Hossai Furmli

    (University of Toronto Scarborough)

  • Dylan M. Owen

    (King’s College London Guy’s Campus)

  • Alexei Savchenko

    (University of Toronto
    University of Calgary)

  • Bebhinn Treanor

    (University of Toronto
    University of Toronto
    University of Toronto Scarborough)

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.

Suggested Citation

  • 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 , 2018. "Galectin-9 binds IgM-BCR to regulate B cell signaling," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05771-8
    DOI: 10.1038/s41467-018-05771-8
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    Cited by:

    1. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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