Biology subjects

Riobo Cavada, I.

Publications and source records attributed to Riobo Cavada, I..

2 recordsLinked to original sources

bioRxiv2026

Coupling lysosomal polarity and purinergic signaling regulates B cell activation

B cell activation is initiated by engagement of the B cell receptor (BCR) with immobilized antigens, which triggers changes in cell polarity promoting the establishment of an immune synapse that is further shaped by signals from the microenvironment. However, how cell polarity coordinates the sensing of extracellular cues to regulate B cell activation remains unclear. Here, we investigated the impact of adenosine triphosphate (ATP), a conventional danger signal related to inflammation, on B cell function. We found that ATP released by B cells, as well as exogenously added ATP, acts as a promoter of the extraction and presentation of immobilized antigens. Endogenous ATP was produced by mitochondria recruited at the immune synapse and locally released via Pannexin 1 channels to sustain purinergic signaling at the immune synapse. We identified P2RX4 trafficking to the plasma membrane through the Rab6a+ trans-Golgi network and VAMP7+/LAMP1+ lysosomes as a key step in this response. In addition, the local activation of P2RX4 at the immune synapse triggered a migratory switch from motile to sessile, suggesting that this receptor acts as a negative regulator of B cell migration. These findings reveal ATP as a local enhancer of B cell function, and an unexpected role of P2RX4 as a molecular switch for B cell activation.

immunology↗

bioRxiv2023

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

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.

cell biology↗