Abstract

B cells extract immobilized antigens via immune synapse formation, a process influenced by the physical properties of the antigen-presenting surface. However, the mechanisms linking mechanotransduction to antigen extraction and processing remain poorly understood. Here, we show that B cells activated on stiff substrates initiate mechanotransduction responses that drive the translocation of the microtubule acetylase ATAT1 from the nucleus to the cytoplasm, leading to increased α-tubulin acetylation. This modification releases GEF-H1 at the immune synapse, where it promotes the formation of actin foci essential for antigen extraction. Acetylated microtubules also enable B cells to stabilize and position lysosomes at the synapse center, thereby coupling actin-dependent extraction to antigen processing and presentation. Accordingly, ATAT1-silenced B cells fail to concentrate actin foci and lysosomes at the synaptic interface, resulting in impaired antigen extraction and presentation to T cells. Overall, these findings underscore how BCR-dependent mechanotransduction induces microtubule modifications to orchestrate lysosome positioning and actin remodeling at the immune synapse.