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

Author

Listed:
  • Julia Merkenschlager

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory)

  • Mickaël J. Ploquin

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory
    Present address: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France)

  • Urszula Eksmond

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory)

  • Rakieb Andargachew

    (Emory University School of Medicine)

  • Georgina Thorborn

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory
    Present address: William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK)

  • Andrew Filby

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory
    Present address: Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK)

  • Marion Pepper

    (University of Washington)

  • Brian Evavold

    (Emory University School of Medicine)

  • George Kassiotis

    (Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory
    Faculty of Medicine, Imperial College London)

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.

Suggested Citation

  • Julia Merkenschlager & Mickaël J. Ploquin & Urszula Eksmond & Rakieb Andargachew & Georgina Thorborn & Andrew Filby & Marion Pepper & Brian Evavold & George Kassiotis, 2016. "Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10281
    DOI: 10.1038/ncomms10281
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    Cited by:

    1. Julia Merkenschlager & Riza-Maria Berz & Victor Ramos & Maximilian Uhlig & Andrew J. MacLean & Carla R. Nowosad & Thiago Y. Oliveira & Michel C. Nussenzweig, 2023. "Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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