%0 Journal Article
%A Fernández Messina, Lola María
%A Rodríguez‐Galán, Ana
%A Yébenes, Virginia de
%A Gutiérrez‐Vázquez, Cristina
%A Tenreiro, Sandra
%A Seabra, Miguel 
%A Ramiro, Almudena 
%A Sánchez‐Madrid, Francisco
%T Transfer of extracellular vesicle‐micro controls germinal center reaction and antibody production
%D 2020
%@ 1469-221X
%U https://hdl.handle.net/20.500.14352/97225
%X Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders.
%~