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B cell antigen extraction is regulated by physical properties of antigen-presenting cells

Antibody production and affinity maturation are driven by B cell extraction and internalization of antigen from immune synapses. However, the extraction mechanism remains poorly understood. Here we develop DNA-based nanosensors to interrogate two previously proposed mechanisms, enzymatic liberation...

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Detalles Bibliográficos
Autores principales: Spillane, Katelyn M., Tolar, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223605/
https://www.ncbi.nlm.nih.gov/pubmed/27923880
http://dx.doi.org/10.1083/jcb.201607064
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author Spillane, Katelyn M.
Tolar, Pavel
author_facet Spillane, Katelyn M.
Tolar, Pavel
author_sort Spillane, Katelyn M.
collection PubMed
description Antibody production and affinity maturation are driven by B cell extraction and internalization of antigen from immune synapses. However, the extraction mechanism remains poorly understood. Here we develop DNA-based nanosensors to interrogate two previously proposed mechanisms, enzymatic liberation and mechanical force. Using antigens presented by either artificial substrates or live cells, we show that B cells primarily use force-dependent extraction and resort to enzymatic liberation only if mechanical forces fail to retrieve antigen. The use of mechanical forces renders antigen extraction sensitive to the physical properties of the presenting cells. We show that follicular dendritic cells are stiff cells that promote strong B cell pulling forces and stringent affinity discrimination. In contrast, dendritic cells are soft and promote acquisition of low-affinity antigens through low forces. Thus, the mechanical properties of B cell synapses regulate antigen extraction, suggesting that distinct properties of presenting cells support different stages of B cell responses.
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spelling pubmed-52236052017-07-02 B cell antigen extraction is regulated by physical properties of antigen-presenting cells Spillane, Katelyn M. Tolar, Pavel J Cell Biol Research Articles Antibody production and affinity maturation are driven by B cell extraction and internalization of antigen from immune synapses. However, the extraction mechanism remains poorly understood. Here we develop DNA-based nanosensors to interrogate two previously proposed mechanisms, enzymatic liberation and mechanical force. Using antigens presented by either artificial substrates or live cells, we show that B cells primarily use force-dependent extraction and resort to enzymatic liberation only if mechanical forces fail to retrieve antigen. The use of mechanical forces renders antigen extraction sensitive to the physical properties of the presenting cells. We show that follicular dendritic cells are stiff cells that promote strong B cell pulling forces and stringent affinity discrimination. In contrast, dendritic cells are soft and promote acquisition of low-affinity antigens through low forces. Thus, the mechanical properties of B cell synapses regulate antigen extraction, suggesting that distinct properties of presenting cells support different stages of B cell responses. The Rockefeller University Press 2017-01-02 /pmc/articles/PMC5223605/ /pubmed/27923880 http://dx.doi.org/10.1083/jcb.201607064 Text en © 2017 Spillane and Tolar http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License(Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Spillane, Katelyn M.
Tolar, Pavel
B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title_full B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title_fullStr B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title_full_unstemmed B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title_short B cell antigen extraction is regulated by physical properties of antigen-presenting cells
title_sort b cell antigen extraction is regulated by physical properties of antigen-presenting cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223605/
https://www.ncbi.nlm.nih.gov/pubmed/27923880
http://dx.doi.org/10.1083/jcb.201607064
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