Spatiotemporal control of microtubule acetylation by mechanical cues regulates lysosome dynamics at the immune synapse of B cells to promote antigen presentation

Abstract

The capacity of B cells to extract immobilized antigens through the formation of an immune synapse can be tuned by the physical characteristics of the surface where antigens are encountered. However, the underlying mechanisms that couple mechanosensing by B cells to antigen extraction and processing remain poorly understood. We show that B cells activated by antigens associated with stiffer substrates exhibit enhanced spreading responses and higher tubulin acetylation at the center of the immune synapse, where less motile lysosomes preferentially localize. This process is coupled to the translocation of the microtubule acetylase, ATAT1 to the cytoplasm of B cells, which occurs as a mechano-response during BCR stimulation. Accordingly, B cells silenced for ATAT1 are unable to stabilize lysosomes at the synaptic interface and display a lower capacity to extract and present immobilized antigens to T cells. Overall, these findings highlight how BCR-dependent mechano-responses trigger microtubule network modifications to precisely orchestrate lysosome positioning to promote antigen extraction and presentation in B cells.