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BCELLMECHANICS SIGNED

Regulation of antibody responses by B cell mechanical activity

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EC-Contrib. €

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Project "BCELLMECHANICS" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙999˙386 €
 EC max contribution 1˙999˙386 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 1˙999˙386.00

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 Project objective

The production of antibodies against pathogens is an effective mechanism of protection against a wide range of infections. However, some pathogens evade antibody responses by rapidly changing their composition. Designing vaccines that elicit antibody responses against invariant parts of the pathogen is a rational strategy to combat existing and emerging pathogens. Production of antibodies is initiated by binding of B cell receptors (BCRs) to foreign antigens presented on the surfaces of antigen presenting cells. This binding induces B cell signalling and internalisation of the antigens for presentation to helper T cells. Although it is known that T cell help controls B cell expansion and differentiation into antibody-secreting and memory B cells, how the strength of antigen binding to the BCR regulates antigen internalisation remains poorly understood. As a result, the response and the affinity maturation of individual B cell clones are difficult to predict, posing a problem for the design of next-generation vaccines. My aim is to develop an understanding of the cellular mechanisms that underlie critical B cell activation steps. My laboratory has recently described that B cells use mechanical forces to extract antigens from antigen presenting cells. We hypothesise that application of mechanical forces tests BCR binding strength and thereby regulates B cell clonal selection during antibody affinity maturation and responses to pathogen evasion. We propose to test this hypothesis by (1) determining the magnitude and timing of the forces generated by B cells, and (2) determining the role of the mechanical properties of BCR-antigen bonds in affinity maturation and (3) in the development of broadly neutralising antibodies. We expect that the results of these studies will contribute to our understanding of the mechanisms that regulate the antibody repertoire in response to infections and have practical implications for the development of vaccines.

 Publications

year authors and title journal last update
List of publications.
2017 Carla R. Nowosad, Pavel Tolar
Plasma Membrane Sheets for Studies of B Cell Antigen Internalization from Immune Synapses.
published pages: 77-88, ISSN: , DOI: 10.1007/978-1-4939-6881-7_6
Methods in Molecular Biology 2020-01-29
2017 Pavel Tolar
Cytoskeletal control of B cell responses to antigens
published pages: 621-634, ISSN: 1474-1733, DOI: 10.1038/nri.2017.67
Nature Reviews Immunology 17/10 2020-01-29
2018 Katelyn M. Spillane, Pavel Tolar
DNA-Based Probes for Measuring Mechanical Forces in Cell-Cell Contacts: Application to B Cell Antigen Extraction from Immune Synapses
published pages: 69-80, ISSN: , DOI: 10.1007/978-1-4939-7474-0_5
Methods in Molecular Biology 2020-01-29
2018 Robbert Hoogeboom, Elizabeth M. Natkanski, Carla R. Nowosad, Dessislava Malinova, Rajesh P. Menon, Antonio Casal, Pavel Tolar
Myosin IIa Promotes Antibody Responses by Regulating B Cell Activation, Acquisition of Antigen, and Proliferation
published pages: 2342-2353, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.04.087
Cell Reports 23/8 2020-01-29
2017 Spillane KM, Tolar P
B cell antigen extraction is regulated by physical properties of antigen-presenting cells
published pages: , ISSN: 0021-9525, DOI: 10.1083/jcb.201607064
Journal of Cell Biology 2020-01-29
2016 Carla R Nowosad, Katelyn M Spillane, Pavel Tolar
Germinal center B cells recognize antigen through a specialized immune synapse architecture
published pages: 870-877, ISSN: 1529-2908, DOI: 10.1038/ni.3458
Nature Immunology 17/7 2020-01-29

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