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首页> 外文期刊>Nature >T-FH-derived dopamine accelerates productive synapses in germinal centres
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T-FH-derived dopamine accelerates productive synapses in germinal centres

机译：T-FH衍生的多巴胺可促进生发中心的生产性突触

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摘要

Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T-FH) 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 T-FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T-FH 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 T-FH 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.
机译：保护性高亲和力抗体反应取决于生发中心的滤泡辅助性T（T-FH）细胞对携带体细胞突变B细胞受体的B细胞的竞争选择。在此过程中发生的快速T-B细胞相互作用使人联想到神经突触传递途径。在这里，我们显示一部分人类T-FH细胞含有以嗜铬粒蛋白B标记的致密颗粒，通常在储存儿茶酚胺（如多巴胺）的神经元突触前末端中发现。 T-FH细胞产生大量的多巴胺，并在与B细胞发生同源相互作用时释放。多巴胺会导致细胞内ICOSL（诱导性T细胞共刺激配体，也称为ICOSLG）快速移位到B细胞表面，从而增强CD40L和嗜铬粒蛋白B颗粒在人T-FH细胞突触中的积累并增加突触。区域。数学模型表明，更快的多巴胺诱导的T-B细胞相互作用增加了生发中心的总输出量，并加快了几天的速度。面对感染，跨T-B细胞突触传递神经递质可能是有利的。

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  • 来源
    《Nature》 |2017年第7663期|318-323|共6页
  • 作者

    Papa Ilenia; Saliba David; Ponzoni Maurilio; Bustamante Sonia; Canete Pablo F.; Gonzalez-Figueroa Paula; McNamara Hayley A.; Valvo Salvatore; Grimbaldeston Michele; Sweet Rebecca A.; Vohra Harpreet; Cockburn Ian A.; Meyer-Hermann Michael; Dustin Michael L.; Doglioni Claudio; Vinuesa Carola G.;

  • 作者单位

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Kennedy Inst Rheumatol, Oxford OX3 7LD, England;

    IRCCS Sci Inst San Raffaele, Dept Pathol, Ateneo Vita Salute, I-20132 Milan, Italy;

    Univ New South Wales, Mark Wainwright Analyt Ctr, Bioanalyt Mass Spectrometry Facil, Sydney, NSW 2052, Australia;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Kennedy Inst Rheumatol, Oxford OX3 7LD, England;

    Univ South Australia, Ctr Canc Biol, Adelaide, SA 5000, Australia|SA Pathol, Adelaide, SA 5000, Australia|Genentech Inc, OMNI Biomarker Dev, San Francisco, CA 94080 USA;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Australian Natl Univ, John Curtin Sch Med Res, Imaging & Cytometry Facil, Canberra, ACT 2601, Australia;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia;

    Helmholtz Ctr Infect Res, Dept Syst Immunol, D-38124 Braunschweig, Germany|Helmholtz Ctr Infect Res, Braunschweig Integrated Ctr Syst Biol, D-38124 Braunschweig, Germany;

    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Kennedy Inst Rheumatol, Oxford OX3 7LD, England;

    IRCCS Sci Inst San Raffaele, Dept Pathol, Ateneo Vita Salute, I-20132 Milan, Italy;

    Australian Natl Univ, John Curtin Sch Med Res, Dept Immunol & Infect Dis, Canberra, ACT 2601, Australia|Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, China Australia Ctr Personalised Immunol, Shanghai 200085, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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