Vamp-7-dependent secretion at the immune synapse regulates antigen extraction and presentation in B-lymphocytes.
Recognition of surface-tethered antigens (Ags) by B-cells leads to the formation of an immune synapse that promotes Ag uptake for presentation onto MHC-II molecules. Extraction of immobilized Ags at the immune synapse of B-cells relies on the local secretion of lysosomes, which are recruited to the Ag contact site by polarization of their microtubule network. Although conserved polarity proteins have been implicated in coordinating cytoskeleton remodeling with lysosome trafficking, the cellular machinery associated with lysosomal vesicles that regulates their docking and secretion at the synaptic interface has not been defined. Here we show that the v-SNARE protein Vamp-7 is associated with Lamp-1+lysosomal vesicles, which are recruited and docked at the center of the immune synapse of B-cells. A decrease in Vamp-7 expression does not alter lysosome transport to the synaptic interface but impairs their local secretion, a defect that compromises the ability of B-cells to extract, process, and present immobilized Ag. Thus our results reveal that B-cells rely on the SNARE protein Vamp-7 to promote the local exocytosis of lysosomes at the immune synapse, which is required for efficient Ag extraction and presentation.
INSERM, U932 Immunité et Cancer, Institut Curie, PSL Research University, 75005 Paris, France.
Dorian
D
Obino
Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Jheimmy
J
Diaz
Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Juan José
JJ
Sáez
Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Jorge
J
Ibañez-Vega
INSERM, U932 Immunité et Cancer, Institut Curie, PSL Research University, 75005 Paris, France.
Pablo J
PJ
Sáez
Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Martina
M
Alamo
INSERM, U932 Immunité et Cancer, Institut Curie, PSL Research University, 75005 Paris, France.
Danielle
D
Lankar
Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile myuseff@bio.puc.cl.
Maria-Isabel
MI
Yuseff
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D005089:Exocytosis; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D021381:Protein Transport; D050683:R-SNARE Proteins / Q000378:metabolism* / Q000502:physiology*; D050600:SNARE Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D000941:Antigens; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C496927:Sybl1 protein, mouse