期刊
EMBO REPORTS
卷 21, 期 4, 页码 -出版社
WILEY
DOI: 10.15252/embr.201948925
关键词
antibody production; exosomes; extracellular vesicles; germinal center (GC) reaction; microRNAs
资金
- Spanish Ministry of Economy and Competitiveness [SAF 2017-82886-R]
- Comunidad de Madrid [S2017/BMD-3671-INFLAMUNE-CM]
- CIBERCV [CB16/11/00272]
- Instituto de Salud Carlos III [BIOIMID PIE13/041]
- Fundacion La Marato TV3 [122/C/2015]
- la Caixa Foundation [HR17-00016]
- AECC foundation
- CNIC funding
- Spanish Ministerio de Ciencia, Innovacion y Universidades [SAF2016-75511-R]
- La Caixa Health Research Program [HR17-00247]
- Ramon Areces Foundation Ciencias de la Vida y de la Salud (XIX Concurso-2018)
- Ayuda Fundacion BBVA y Equipo de Investigacion Cientifica (BIOMEDICINA-2018)
- Ministerio de Ciencia, Innovacion y Universidades
- Pro-CNIC Foundation
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.
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