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Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells

B-cell receptor (BCR)-mediated antigen internalization and presentation are essential for humoral memory immune responses. Antigen encountered by B-cells is often tightly associated with the surface of pathogens and/or antigen-presenting cells. Internalization of such antigens requires myosin-mediat...

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Autores principales: Maeda, Fernando Y, van Haaren, Jurriaan JH, Langley, David B, Christ, Daniel, Andrews, Norma W, Song, Wenxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589448/
https://www.ncbi.nlm.nih.gov/pubmed/34704555
http://dx.doi.org/10.7554/eLife.66984
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author Maeda, Fernando Y
van Haaren, Jurriaan JH
Langley, David B
Christ, Daniel
Andrews, Norma W
Song, Wenxia
author_facet Maeda, Fernando Y
van Haaren, Jurriaan JH
Langley, David B
Christ, Daniel
Andrews, Norma W
Song, Wenxia
author_sort Maeda, Fernando Y
collection PubMed
description B-cell receptor (BCR)-mediated antigen internalization and presentation are essential for humoral memory immune responses. Antigen encountered by B-cells is often tightly associated with the surface of pathogens and/or antigen-presenting cells. Internalization of such antigens requires myosin-mediated traction forces and extracellular release of lysosomal enzymes, but the mechanism triggering lysosomal exocytosis is unknown. Here, we show that BCR-mediated recognition of antigen tethered to beads, to planar lipid-bilayers or expressed on cell surfaces causes localized plasma membrane (PM) permeabilization, a process that requires BCR signaling and non-muscle myosin II activity. B-cell permeabilization triggers PM repair responses involving lysosomal exocytosis, and B-cells permeabilized by surface-associated antigen internalize more antigen than cells that remain intact. Higher affinity antigens cause more B-cell permeabilization and lysosomal exocytosis and are more efficiently presented to T-cells. Thus, PM permeabilization by surface-associated antigen triggers a lysosome-mediated B-cell resealing response, providing the extracellular hydrolases that facilitate antigen internalization and presentation.
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spelling pubmed-85894482021-11-15 Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells Maeda, Fernando Y van Haaren, Jurriaan JH Langley, David B Christ, Daniel Andrews, Norma W Song, Wenxia eLife Cell Biology B-cell receptor (BCR)-mediated antigen internalization and presentation are essential for humoral memory immune responses. Antigen encountered by B-cells is often tightly associated with the surface of pathogens and/or antigen-presenting cells. Internalization of such antigens requires myosin-mediated traction forces and extracellular release of lysosomal enzymes, but the mechanism triggering lysosomal exocytosis is unknown. Here, we show that BCR-mediated recognition of antigen tethered to beads, to planar lipid-bilayers or expressed on cell surfaces causes localized plasma membrane (PM) permeabilization, a process that requires BCR signaling and non-muscle myosin II activity. B-cell permeabilization triggers PM repair responses involving lysosomal exocytosis, and B-cells permeabilized by surface-associated antigen internalize more antigen than cells that remain intact. Higher affinity antigens cause more B-cell permeabilization and lysosomal exocytosis and are more efficiently presented to T-cells. Thus, PM permeabilization by surface-associated antigen triggers a lysosome-mediated B-cell resealing response, providing the extracellular hydrolases that facilitate antigen internalization and presentation. eLife Sciences Publications, Ltd 2021-10-27 /pmc/articles/PMC8589448/ /pubmed/34704555 http://dx.doi.org/10.7554/eLife.66984 Text en © 2021, Maeda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Maeda, Fernando Y
van Haaren, Jurriaan JH
Langley, David B
Christ, Daniel
Andrews, Norma W
Song, Wenxia
Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title_full Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title_fullStr Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title_full_unstemmed Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title_short Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
title_sort surface-associated antigen induces permeabilization of primary mouse b-cells and lysosome exocytosis facilitating antigen uptake and presentation to t-cells
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589448/
https://www.ncbi.nlm.nih.gov/pubmed/34704555
http://dx.doi.org/10.7554/eLife.66984
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