TY - JOUR
T1 - Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production
AU - Fernández-Messina, Lola
AU - Rodríguez-Galán, Ana
AU - de Yébenes, Virginia G.
AU - Gutiérrez-Vázquez, Cristina
AU - Tenreiro, Sandra
AU - Seabra, Miguel C.
AU - Ramiro, Almudena R.
AU - Sánchez-Madrid, Francisco
PY - 2020/4/3
Y1 - 2020/4/3
N2 - 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.
AB - 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.
KW - antibody production
KW - exosomes
KW - extracellular vesicles
KW - germinal center (GC) reaction
KW - microRNAs
UR - http://www.scopus.com/inward/record.url?scp=85079788058&partnerID=8YFLogxK
U2 - 10.15252/embr.201948925
DO - 10.15252/embr.201948925
M3 - Article
C2 - 32073750
AN - SCOPUS:85079788058
JO - Embo Reports
JF - Embo Reports
SN - 1469-221X
M1 - e48925
ER -