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Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility

Maro Iliopoulou, Anna T. Bajur, Hannah C. W. McArthur, Carl Coyle, Favour Ajao, Robert Köchl, Andrew P. Cope, Katelyn M. Spillane
doi: https://doi.org/10.1101/2022.12.02.518873
Maro Iliopoulou
1Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
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Anna T. Bajur
1Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
2Randall Centre for Cell & Molecular Biophysics, King’s College London, London SE1 1UL, United Kingdom
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Hannah C. W. McArthur
1Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
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Carl Coyle
3Centre for Inflammation Biology and Cancer Immunology, King’s College London, London SE1 1UL, United Kingdom
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Favour Ajao
1Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
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Robert Köchl
4Peter Gorer Department of Immunobiology, King’s College London, London SE1 1UL, United Kingdom
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Andrew P. Cope
3Centre for Inflammation Biology and Cancer Immunology, King’s College London, London SE1 1UL, United Kingdom
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Katelyn M. Spillane
1Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
2Randall Centre for Cell & Molecular Biophysics, King’s College London, London SE1 1UL, United Kingdom
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  • For correspondence: katelyn.spillane@kcl.ac.uk
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Abstract

Subcapsular sinus macrophages (SSMs) play a key role in immune defence by forming immunological barriers that control the transport of pathogens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal centre reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multi-colour fluorescence microscopy to identify lymph nodederived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells and found that their actin cytoskeleton regulates the spatial organisation and mobility of immune complexes displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix (ECM) rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and immune complex mobility. Our results reveal a new mechanism regulating physical aspects of antigen presentation by antigen-presenting cells, which may have implications for B cell activation and antibody responses.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 03, 2022.
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Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility
Maro Iliopoulou, Anna T. Bajur, Hannah C. W. McArthur, Carl Coyle, Favour Ajao, Robert Köchl, Andrew P. Cope, Katelyn M. Spillane
bioRxiv 2022.12.02.518873; doi: https://doi.org/10.1101/2022.12.02.518873
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Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility
Maro Iliopoulou, Anna T. Bajur, Hannah C. W. McArthur, Carl Coyle, Favour Ajao, Robert Köchl, Andrew P. Cope, Katelyn M. Spillane
bioRxiv 2022.12.02.518873; doi: https://doi.org/10.1101/2022.12.02.518873

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