Key Points
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The cortical actin cytoskeleton regulates cellular mechanics and signalling by plasma membrane receptors.
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In B cells, the cortical cytoskeleton is controlled through multiple connections to the signalling pathways that are downstream of the B cell antigen receptor.
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Cortical actin regulates B cell signalling by controlling the diffusion and reaction rates of plasma membrane proteins.
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The remodelling of cortical actin in response to antigen regulates B cell immune synapses, antigen internalization and cell polarization.
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Mechanical forces produced by the cytoskeleton promote affinity discrimination during B cell antigen extraction from antigen-presenting cells.
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Differences in actin dynamics in different B cell subsets contribute to the subset-specific regulation of B cell activation; for example, actin dynamics improve affinity discrimination in germinal centre B cells.
Abstract
The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses.
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Acknowledgements
This work was supported by the H2020 European Research Council (Consolidator Grant 648228) and the Francis Crick Institute (London, UK), which receives its core funding from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. The author thanks members of his laboratory for critical reading of the manuscript and J. Tolar for help with designing the Figures.
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FURTHER INFORMATION
Glossary
- Wiskott–Aldrich syndrome
-
An X-linked primary immunodeficiency, which is characterized by recurrent infections, bleeding disorders, eczema and autoimmune reactions.
- Coronins
-
Proteins that disassemble branched actin filaments. Coronin 1A is the target of mutations that cause primary immunodeficiencies.
- Filopodia
-
Long thin cellular extensions that contain linear actin filaments and are used in cellular sensing and migration.
- Lamellipodia
-
Large flat cellular protrusions containing branched actin filaments that drive cell motility.
- CD81
-
A palmitoylated, cholesterol-binding tetraspanin membrane protein that is essential for CD19 expression and function.
- Active gel theory
-
An area of soft-matter physics that describes the mesoscopic behaviour of gels (such as those composed of actin filaments) that are maintained in a non-equilibrium state by the constant consumption of energy.
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Tolar, P. Cytoskeletal control of B cell responses to antigens. Nat Rev Immunol 17, 621–634 (2017). https://doi.org/10.1038/nri.2017.67
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DOI: https://doi.org/10.1038/nri.2017.67
