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

Elife. 2019 Dec 9:8:e48093. doi: 10.7554/eLife.48093.

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.

Keywords: B cell; B cell receptor; actin cytoskeleton; antigen; cell biology; endocytosis; human; immune synapse; immunology; inflammation; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / immunology*
  • Actin Cytoskeleton / metabolism
  • Actin-Related Protein 2-3 Complex / immunology*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / immunology*
  • Actins / metabolism
  • Animals
  • Antibody Formation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens / immunology*
  • Antigens / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Immunological Synapses / immunology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Antigens
  • Receptors, Antigen, B-Cell

Associated data

  • GEO/GSE72019