Cytoskeletal control of B cell responses to antigens

Tolar, Pavel

doi:10.1038/nri.2017.67

Cited by 118 publications

(102 citation statements)

References 183 publications

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“…In this review, we discuss how B cell synapse formation is coordinated within the lymph node and how the molecular components that link antigens to both the B cell and the APC mechanically regulate B cell responses to antigen. Cellular forces are generated by the actomyosin cytoskeleton and the molecular components of the cytoskeletal machinery and dynamics of actin-driven immune synapse formation have recently been reviewed in detail [19]. Here, we will examine how forces in the immune synapse influence the lifetime of molecular bonds involving the BCR, antigen, complexing antibodies, complement fragments, and membrane receptors that display antigens on the APC surface.…”

Section: Introductionmentioning

confidence: 99%

Mechanics of antigen extraction in the B cell synapse

Spillane

Tolar

2018

Molecular Immunology

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B cell encounter with antigen displayed on antigen-presenting cells leads to B cell immune synapse formation, internalisation of the antigen, and stimulation of antibody responses. The sensitivity with which B cells detect antigen, and the quality and quantity of antigen that B cells acquire, depend upon mechanical properties of the immune synapse including interfacial tension, the strength of intermolecular bonds, and the compliance of the molecules and membranes that participate in antigen presentation. In this review, we discuss our current understanding of how these various physical parameters influence B cell antigen extraction in the immune synapse and how a more comprehensive understanding of B cell mechanics may promote the development of new approaches to stimulate the production of desired antibodies.

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Section: Introductionmentioning

confidence: 99%

Mechanics of antigen extraction in the B cell synapse

Spillane

Tolar

2018

Molecular Immunology

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“…This information can be used to better understand the role of Factin not just in B cell antigen endocytosis, but also in receptor signaling at the plasma membrane. The organization of the BCR, and other signaling receptors on B cell surfaces critically depend on actin structure (Mattila et al, 2016) and defects in actin polymerization contribute to the dysregulation of signaling in primary immunodeficiencies and in autoimmunity (Tolar, 2017). Our studies should guide future investigations of the regulation Arp2/3 and formin pathways in B cells in this context.…”

Section: Discussionmentioning

confidence: 83%

B cells extract antigens using Arp2/3-generated actin foci interspersed with linear filaments

Roper

Wasim

Malinova

et al. 2019

Preprint

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Antibody production depends on B cell internalization and presentation of antigens to helper T cells. To acquire antigens displayed by antigen-presenting cells, B cells form immune synapses and extract antigens by the mechanical activity of the acto-myosin cytoskeleton.While cytoskeleton organization driving the initial formation of the B cell synapse has been studied, how the cytoskeleton supports antigen extraction remains poorly understood. Here we show that after initial cell spreading, F-actin in B cell synapses forms a highly dynamic pattern composed of actin foci interspersed with linear filaments and myosin IIa. The foci are generated by Arp2/3-mediated branched-actin polymerization and stochastically associate with antigen clusters to mediate internalization. However, antigen extraction also requires the activity of formins, which reside near the foci and produce the interspersed filaments. Thus, a cooperation of branched-actin foci supported by linear filaments underlies B cell mechanics during antigen extraction.

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“…37 (Figure 2). 39 We further speculate that the differentiation of atypical MBCs refractory to soluble antigen may be a mechanism to dampen chronic B cell stimulation by high concentrations of low molecular weight soluble antigens that can enter follicles directly 40,41 and may persist during chronic infections.…”

Section: The Fun C Ti On Of Mal Aria-a Sso Ciated At Ypi C Al Mbc Smentioning

confidence: 85%

Exhaustion may not be in the human B cell vocabulary, at least not in malaria

Holla

Ambegaonkar

Sohn

et al. 2019

Immunological Reviews

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T cells exposed to persistent antigen in the inflammatory environment of chronic infections often show progressive loss of effector functions, high expression of inhibitory receptors and distinct transcriptional programs. T cells in this functional state are termed “exhausted” and T cell exhaustion is associated with inefficient control of infections. A remarkably similar scenario has been described for B cells during chronic infections in humans, including malaria, in which case a subpopulation of atypical memory B cells (MBCs) greatly expands and these MBCs show attenuation of B cell receptor signaling, loss of the B cell effector functions of antibody and cytokine production, high expression of inhibitory receptors and distinct transcriptional profiles. The expansion of these MBCs is also associated with inefficient control of infections. Despite the similarities with exhausted T cells we speculate that at least in malaria, atypical MBCs may not be exhausted but rather may be functional, possibly even beneficial. Our recent results suggest that we simply may not have known how to ask an atypical MBC to function. Thus, exhaustion may not be in the human B cell's vocabulary, at least not in malaria.

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Cytoskeletal control of B cell responses to antigens

Cited by 118 publications

References 183 publications

Mechanics of antigen extraction in the B cell synapse

Mechanics of antigen extraction in the B cell synapse

B cells extract antigens using Arp2/3-generated actin foci interspersed with linear filaments

Exhaustion may not be in the human B cell vocabulary, at least not in malaria

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