title: Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.
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.
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Merkenschlager
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Mickaël J
authors.initials: MJ
authors.lastname: Ploquin
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Urszula
authors.initials: U
authors.lastname: Eksmond
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Rakieb
authors.initials: R
authors.lastname: Andargachew
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Thorborn
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Filby
authors.affiliation: Department of Immunology, University of Washington, Seattle, Washington 98109-8059, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Pepper
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Evavold
authors.affiliation: Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.|Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK.
authors.forename: George
authors.initials: G
authors.lastname: Kassiotis
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002999:Clone Cells / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*