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Transfer of extracellular vesicle‐micro RNA controls germinal center reaction and antibody production

2020; Springer Nature; Volume: 21; Issue: 4 Linguagem: Inglês

10.15252/embr.201948925

1469-3178

Lola Fernández‐Messina, Ana Rodríguez‐Galán, Virginia G. de Yébenes, Cristina Gutiérrez‐Vázquez, Sandra Tenreiro, Miguel C. Seabra, Almudena R. Ramiro, Francisco Sánchez‐Madrid,

Systemic Lupus Erythematosus Research

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.