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EMBO Rep. 2020 Apr 3;21(4):e48925. doi: 10.15252/embr.201948925. Epub 2020 Feb 19.

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

Author information

1
Immunology Service, Hospital de la Princesa, Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
2
Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
3
Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
4
B lymphocyte Biology Lab, Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
5
CEDOC, Faculdade de Ciências Médicas, Chronic Diseases Research Centre, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal.

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.

KEYWORDS:

antibody production; exosomes; extracellular vesicles; germinal center (GC) reaction; microRNAs

PMID:
32073750
DOI:
10.15252/embr.201948925

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