Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

• Type of Material: Article
• Authors: Julia Merkenschlager, Francis Crick Institute; Mickaël J. Ploquin, Francis Crick Institute; Urszula Eksmond, Francis Crick Institute; Rakieb Andargachew, Emory University; Georgina Thorborn, Francis Crick Institute; Andrew Filby, Francis Crick Institute; Marion Pepper, University of Washington; Brian Evavold, Emory University; George Kassiotis, Francis Crick Institute
• Language: English
• Date: 2016-01-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2016, Nature Publishing Group.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms10281
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 7
• Start Page: 10281
• End Page: 10281
• Grant/Funding Information: This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK, the UK Medical Research Council (U117581330 to G.K.), and the Wellcome Trust.
• Keywords: Multidisciplinary Sciences; B cells; Science & Technology; Viral infection; CD4-positive T cells; Cell death and immune response
• Research Categories: Health Sciences, Immunology

Abstract

Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4+ T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4+ T-cell response also to vaccination or tumour challenge, revealing a common effect.