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TFH-derived dopamine accelerates productive synapses in germinal centres

Author

Listed:
  • Ilenia Papa

    (John Curtin School of Medical Research, Australian National University)

  • David Saliba

    (Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford)

  • Maurilio Ponzoni

    (Ateneo Vita-Salute, IRCCS Scientific Institute San Raffaele)

  • Sonia Bustamante

    (Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales)

  • Pablo F. Canete

    (John Curtin School of Medical Research, Australian National University)

  • Paula Gonzalez-Figueroa

    (John Curtin School of Medical Research, Australian National University)

  • Hayley A. McNamara

    (John Curtin School of Medical Research, Australian National University)

  • Salvatore Valvo

    (Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford)

  • Michele Grimbaldeston

    (Centre for Cancer Biology, University of South Australia and SA Pathology
    OMNI-Biomarker Development, Genentech Inc., South San Francisco)

  • Rebecca A. Sweet

    (John Curtin School of Medical Research, Australian National University)

  • Harpreet Vohra

    (Imaging and Cytometry Facility, John Curtin School of Medical Research, Australian National University)

  • Ian A. Cockburn

    (John Curtin School of Medical Research, Australian National University)

  • Michael Meyer-Hermann

    (Helmholtz Centre for Infection Research)

  • Michael L. Dustin

    (Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford)

  • Claudio Doglioni

    (Ateneo Vita-Salute, IRCCS Scientific Institute San Raffaele)

  • Carola G. Vinuesa

    (John Curtin School of Medical Research, Australian National University
    China-Australia Centre for Personalised Immunology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine)

Abstract

Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (TFH) cells in germinal centres. The rapid T–B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human TFH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. TFH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human TFH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T–B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T–B-cell synapse may be advantageous in the face of infection.

Suggested Citation

  • Ilenia Papa & David Saliba & Maurilio Ponzoni & Sonia Bustamante & Pablo F. Canete & Paula Gonzalez-Figueroa & Hayley A. McNamara & Salvatore Valvo & Michele Grimbaldeston & Rebecca A. Sweet & Harpree, 2017. "TFH-derived dopamine accelerates productive synapses in germinal centres," Nature, Nature, vol. 547(7663), pages 318-323, July.
    • Handle: RePEc:nat:nature:v:547:y:2017:i:7663:d:10.1038_nature23013
    DOI: 10.1038/nature23013
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