1. TFH-derived dopamine accelerates productive synapses in germinal centres
- Author
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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, and Vinuesa, Carola G.
- Subjects
Synapses -- Physiological aspects ,Dopamine -- Physiological aspects ,T cells -- Physiological aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T[sub.FH]) cells in germinal centres. The rapid TB-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T[sub.FH] cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T[sub.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[sub.FH] cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced TB-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the TB-cell synapse may be advantageous in the face of infection., Author(s): Ilenia Papa [1]; David Saliba [2]; Maurilio Ponzoni [3]; Sonia Bustamante [4]; Pablo F. Canete [1]; Paula Gonzalez-Figueroa [1]; Hayley A. McNamara [1]; Salvatore Valvo [2]; Michele Grimbaldeston [5, [...]
- Published
- 2017
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