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

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

doi:10.1038/s41467-018-05771-8

Cited by 85 publications

(110 citation statements)

References 70 publications

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“…Although Galectin-8 does not form multivalent oligomers as Galectin-3, a non-quantitative proteomic analysis of Galectin-8 binding partners in B cells revealed that Galectin-8 interacts directly with the BCR ( Table S1 ), which was also supported by a pull-down assay showing that Galectin-8 binds to the BCR. Analogously, Galectin-9 was recently shown to interact directly with the BCR and CD45 and to suppress BCR downstream signaling by restricting the lateral mobility of the receptor and favoring its association with inhibitory molecules ( Cao et al., 2018 ). In contrast to the effect of Galectin-9, we did not observe an inhibition of BCR signaling in the presence of Galectin-8.…”

Section: Discussionmentioning

confidence: 99%

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

Obino¹,

Soza²,

Malbec³

et al. 2018

Cell Reports

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SummaryComplete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8—a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins—is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Galectin-8 triggers a faster recruitment and secretion of lysosomes toward the B cell-antigen contact site, resulting in efficient extraction of immobilized antigens through a proteolytic mechanism. Thus, extracellular cues can determine how B cells sense and extract tethered antigens and thereby tune B cell responses in vivo.

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Section: Discussionmentioning

confidence: 99%

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

Obino¹,

Soza²,

Malbec³

et al. 2018

Cell Reports

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“…Extracellular Galectin-9 has been implicated in inhibiting T cell immunity by promoting T cell apoptosis and differentiation into regulatory T cells (Anderson et al, 2007;Bi et al, 2008;Zhu et al, 2005). Furthermore, extracellular Galectin-9 acts as a suppressor of B cell signalling via binding to the B cell receptor (Cao et al, 2018;Giovannone et al, 2018). While these studies indicate that Galectin-9 plays an inhibitory role on lymphocytes, its function in myeloid cells remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Cano

Tagit

Duffelen

et al. 2019

Preprint

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Extracellular Galectins constitute a novel mechanism of membrane protein organisation at the cell surface. Although Galectins are also highly expressed intracellularly, their cytosolic functions are poorly understood. Here, we investigated the role of Galectin-9 in dendritic cell (DC) surface organisation and function. By combining functional, super-resolution and atomic force microscopy experiments to analyse membrane stiffness, we identified intracellular Galectin-9 to be indispensable for plasma membrane integrity and structure in DCs. Galectin-9 knockdown studies revealed intracellular Galectin-9 to directly control cortical membrane structure via modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organisation. Consequent to its role in maintaining plasma membrane structure, phagocytosis studies revealed that Galectin-9 was essential for C-type lectin receptor-mediated pathogen uptake by human DCs. This was confirmed by the impaired phagocytic capacity of Galectin-9-null murine DCs. Together, this study demonstrates a novel role for intracellular Galectin-9 in modulating DC function, which may be evolutionary conserved.

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“…CD22 function as inhibitor of BCR signaling is hampered by removing five of its 12 glycosylation sites (Wasim et al, 2019). These glycans on CD22 may be bound by Galectin-9 and crosslinked with the BCR, thus explaining the inhibitory function of CD22 and Galectin-9 on BCR signaling (Cao et al, 2018;Wasim et al, 2019). Labeling specific glycan structures for microscopy or flow cytometry.…”

Section: Immune Signalingmentioning

confidence: 99%

Biological and Technical Challenges in Unraveling the Role of N-Glycans in Immune Receptor Regulation

et al. 2020

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N-glycosylation of membrane receptors is important for a wide variety of cellular processes. In the immune system, loss or alteration of receptor glycosylation can affect pathogen recognition, cell-cell interaction, and activation as well as migration. This is not only due to aberrant folding of the receptor, but also to altered lateral mobility or aggregation capacity. Despite increasing evidence of their biological relevance, glycosylation-dependent mechanisms of receptor regulation are hard to dissect at the molecular level. This is due to the intrinsic complexity of the glycosylation process and high diversity of glycan structures combined with the technical limitations of the current experimental tools. It is still challenging to precisely determine the localization and site-occupancy of glycosylation sites, glycan micro-and macro-heterogeneity at the individual receptor level as well as the biological function and specific interactome of receptor glycoforms. In addition, the tools available to manipulate N-glycans of a specific receptor are limited. Significant progress has however been made thanks to innovative approaches such as glycoproteomics, metabolic engineering, or chemoenzymatic labeling. By discussing examples of immune receptors involved in pathogen recognition, migration, antigen presentation, and cell signaling, this Mini Review will focus on the biological importance of N-glycosylation for receptor functions and highlight the technical challenges for examination and manipulation of receptor N-glycans.

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

Cited by 85 publications

References 70 publications

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Biological and Technical Challenges in Unraveling the Role of N-Glycans in Immune Receptor Regulation

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