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Transfer of extracellular vesicle‐micro RNA controls germinal center reaction and antibody production
Author(s) -
FernándezMessina Lola,
RodríguezGalán Ana,
de Yébenes Virginia G,
GutiérrezVázquez Cristina,
Tenreiro Sandra,
Seabra Miguel C,
Ramiro Almudena R,
SánchezMadrid Francisco
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948925
Subject(s) - germinal center , extracellular vesicle , extracellular , extracellular vesicles , rna , microbiology and biotechnology , chemistry , antibody , biology , biochemistry , microvesicles , gene , genetics , microrna , b cell
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 micro RNA s, 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‐micro RNA s (mmu‐miR20‐a‐5p, mmu‐miR‐25‐3p, and mmu‐miR‐155‐3p) to the B cell. Transferred EV‐micro RNA s target key genes that control B‐cell function, including pro‐apoptotic BIM and the cell cycle regulator PTEN . EV‐micro RNA s transferred during T‐B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27 KO 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‐micro RNA s 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.