5 years ago

TFH-derived dopamine accelerates productive synapses in germinal centres

TFH-derived dopamine accelerates productive synapses in germinal centres
Ilenia Papa, Michael Meyer-Hermann, Rebecca A. Sweet, Paula Gonzalez-Figueroa, Maurilio Ponzoni, Claudio Doglioni, Michele Grimbaldeston, David Saliba, Sonia Bustamante, Ian A. Cockburn, Harpreet Vohra, Michael L. Dustin, Carola G. Vinuesa, Pablo F. Canete, Salvatore Valvo, Hayley A. McNamara
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.

Publisher URL: http://dx.doi.org/10.1038/nature23013

DOI: 10.1038/nature23013

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