title: B cell antigen extraction is regulated by physical properties of antigen-presenting cells.
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.
authors.affiliation: Immune Receptor Activation Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK.|Division of Immunology and Inflammation, Imperial College London, London SW7 2AZ, England, UK.
authors.forename: Katelyn M
authors.identifier: http://orcid.org/0000-0001-8022-4917
authors.initials: KM
authors.lastname: Spillane
authors.affiliation: Immune Receptor Activation Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK pavel.tolar@crick.ac.uk.|Division of Immunology and Inflammation, Imperial College London, London SW7 2AZ, England, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Tolar
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015374:Biosensing Techniques; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism*; D004548:Elasticity; D005260:Female; D005838:Genotype; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036103:Nanotechnology / Q000379:methods; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D000941:Antigens; D007145:Immunoglobulin kappa-Chains; D011947:Receptors, Antigen, B-Cell