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

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Title: B cell antigen extraction is regulated by physical properties of antigen-presenting cells
Authors: Spillane, KM
Tolar, P
Item Type: Journal Article
Abstract: 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.
Issue Date: 6-Dec-2016
Date of Acceptance: 17-Nov-2016
URI: http://hdl.handle.net/10044/1/44996
DOI: https://dx.doi.org/10.1083/jcb.201607064
ISSN: 1540-8140
Publisher: Rockefeller University Press
Start Page: 217
End Page: 230
Journal / Book Title: Journal of Cell Biology
Volume: 216
Issue: 1
Copyright Statement: © 2017 Spillane and Tolar 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 /).
Sponsor/Funder: European Research Council
Funder's Grant Number: Consolidator grant 648228
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
FOLLICULAR DENDRITIC CELLS
IMMUNE-COMPLEXES
GERMINAL CENTER
LYMPH-NODE
AFFINITY DISCRIMINATION
SUBCAPSULAR SINUS
ACTIVATION
SYNAPSE
LYSOSOMES
DYNAMICS
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine (up to 2019)