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

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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.

The following previously published data sets were used

(2016) Long non-coding RNAs in B cells
NCBI Gene Expression Omnibus, GSE72019).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72019
1. Klijn et al
(2015) A comprehensive transcriptional portrait of human cancer cell lines
European Genome-phenome Archive (EGA): EGAS00001000610.

https://www.ebi.ac.uk/ega/studies/EGAS00001000610

Article and author information

Author details

Sophie Isabel Roper

Immune Receptor Activation Laboratory, Francis Crick Institute, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Laabiah Wasim

Immune Receptor Activation Laboratory, Francis Crick Institute, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Dessislava Malinova

Immune Receptor Activation Laboratory, Francis Crick Institute, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Michael Way

Cellular Signalling and Cytoskeletal Function Laboratory, Francis Crick Institute, london, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7207-2722
Susan Cox

Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Pavel Tolar

Immune Receptor Activation Laboratory, Francis Crick Institute, London, United Kingdom

For correspondence
pavel.tolar@crick.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4693-7299

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

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.