Abstract
An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules and information. Although mechanics has been shown to play an important role in this process, how forces organize and impact on synapse function is unknown. We find that mechanical forces are spatio-temporally patterned at the immune synapse: global pulsatile myosin II-driven tangential forces are observed at the synapse periphery while localised forces generated by invadosome-like F-actin protrusions are detected at its centre. Noticeably, we observe that these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis and require myosin II contractility to form. The interplay between global and local forces dictated by the organization of the actomyosin cytoskeleton therefore controls endocytosis at the immune synapse.
Highlights
An important channel of cell-to-cell communication is direct contact
We show that they display a stereotypical patterning profile that includes two components: (1) peripheral forces resulting from the centripetal flow of myosin II and (2) central forces exerted by local invadosome-like actin protrusions, which mediate antigen extraction
Primary naive B cells freshly purified from the spleen of mice expressing a hen egg lysozyme (HEL)-specific B-cell-antigen receptor (BCR) were plated on gels coated with HEL or with bovine serum albumin (BSA) as a negative control
Summary
An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules and information. As endocytosis often involves surface-tethered rather than soluble molecules when occurring in tissues, antigen internalization at the B-cell synapse provides a valuable model to study the impact of mechanics in this process. A second model arose from Atomic Force Microscopy experiments monitoring interactions between the BCR and plasma membrane sheet-bound antigens These experiments showed that B cells internalize these antigens by actively pulling on BCR-antigen complexes[8]. We investigate the spatio-temporal organization of forces exerted by B lymphocytes during antigen extraction We show that they display a stereotypical patterning profile that includes two components: (1) peripheral forces resulting from the centripetal flow of myosin II and (2) central forces exerted by local invadosome-like actin protrusions, which mediate antigen extraction. Myosin II-dependent force patterning emerges as a key regulator of cell–cell interactions
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