eLife · 2019 · 44 citations · 30 references
Life SciencesCell BiologyImmunologyCellular ImmunologyCytoskeletonEndocytosisActin FilamentsActin PolymerizationB Cell BiologyCytoskeletal DynamicsCytoskeleton DynamicsImmune SynapseActin Cytoskeleton DynamicsActin DynamicsActin Polymerization DynamicsAntigen Presenting CellsB Cell Immune SynapseCell InternalizationCell SpreadingSpatial Organization Of Cytoskeleton
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 synapses of primary mouse B cells and human B cell lines 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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