Coupling lysosomal polarity and purinergic signaling regulates B cell activation
Abstract
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.
Related
- A Cilia-Centered Nicotinamide Adenine Dinucleotide (NAD⁺) Signaling Network Regulates Hypothalamic Lysosomal Homeostasis and Metabolic Aging.
- Astrocytic sEH-EET signaling regulates microglial lysosomal function and suppresses the STING-Type I interferon pathway in Alzheimer's disease
- Lysosomal Glycosaminoglycan Catabolism Regulates Microglial Cell State in the Developing CNS
- PCDH17 regulates lysosomal degradative capacity to promote autophagy attenuation during prolonged starvation
- MAPT regulates autophagic-lysosomal function and phagocytosis in human microglia
BibTeX
@misc{rollandi2026coupling,
title = {{Coupling lysosomal polarity and purinergic signaling regulates B cell activation}},
author = {M. Alamo Rollandi and J. P. Bozo and I. Riobo Cavada and T. Lopez-Lopez and J. M. Kux and M. Jaeckstein and B. Rissiek and J. Heeren and D. Sauma and P. J. Saez and M. I. Yuseff},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751411},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751411v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Coupling lysosomal polarity and purinergic signaling regulates B cell activation
AU - M. Alamo Rollandi
AU - J. P. Bozo
AU - I. Riobo Cavada
AU - T. Lopez-Lopez
AU - J. M. Kux
AU - M. Jaeckstein
AU - B. Rissiek
AU - J. Heeren
AU - D. Sauma
AU - P. J. Saez
AU - M. I. Yuseff
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751411
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751411v1
AB - 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.
ER -