B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Long non-coding RNAs in B cellsNCBI Gene Expression Omnibus, GSE72019).
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A comprehensive transcriptional portrait of human cancer cell linesEuropean Genome-phenome Archive (EGA): EGAS00001000610.
Article and author information
Author details
Funding
Francis Crick Institute (FC001185)
- Laabiah Wasim
- Dessislava Malinova
- Pavel Tolar
H2020 European Research Council (648228)
- Dessislava Malinova
- Pavel Tolar
Francis Crick Institute (FC001209)
- Michael Way
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were bred and treated in accordance with guidelines set by the UK Home Office (project license number 7008844) and the Francis Crick Institute Ethical Review Panel.
Copyright
© 2019, Roper et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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