Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production.

Abstract:

: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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Fernández-Messina L,Rodríguez-Galán A,de Yébenes VG,Gutiérrez-Vázquez C,Tenreiro S,Seabra MC,Ramiro AR,Sánchez-Madrid F

doi

10.15252/embr.201948925

subject

Has Abstract

pub_date

2020-04-03 00:00:00

pages

e48925

issue

4

eissn

1469-221X

issn

1469-3178

journal_volume

21

pub_type

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