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Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes

Immune synapse formation is a key step for lymphocyte activation. In B lymphocytes, the immune synapse controls the production of high-affinity antibodies, thereby defining the efficiency of humoral immune responses. While the key roles played by both the actin and microtubule cytoskeletons in the f...

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Published in:eLife 2022-09, Vol.11
Main Authors: Pineau, Judith, Pinon, Léa, Mesdjian, Olivier, Fattaccioli, Jacques, Lennon Duménil, Ana-Maria, Pierobon, Paolo
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description Immune synapse formation is a key step for lymphocyte activation. In B lymphocytes, the immune synapse controls the production of high-affinity antibodies, thereby defining the efficiency of humoral immune responses. While the key roles played by both the actin and microtubule cytoskeletons in the formation and function of the immune synapse have become increasingly clear, how the different events involved in synapse formation are coordinated in space and time by actin–microtubule interactions is not understood. Using a microfluidic pairing device, we studied with unprecedented resolution the dynamics of the various events leading to immune synapse formation and maintenance in murine B cells. Our results identify two groups of events, local and global, dominated by actin and microtubules dynamics, respectively. They further highlight an unexpected role for microtubules and the GEF-H1-RhoA axis in restricting F-actin polymerization at the lymphocyte–antigen contact site, thereby allowing the formation and maintenance of a unique competent immune synapse.
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subjects Actin
Adaptive immunology
Antigens
B lymphocytes
Biochemistry, Molecular Biology
Biophysics
Cell activation
Cell Biology
cell polarity
Cellular Biology
Cytoskeleton
Experiments
GEF-H1
Immune response (humoral)
immune synapse
Immunology
Immunology and Inflammation
Life Sciences
Ligands
Lymphocytes
Lymphocytes B
Microfluidics
Microtubules
Polymerization
RhoA protein
Subcellular Processes
Synapses
title Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes
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