Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation

作     者：Yim, Kevin Ho Wai Al Hrout, Ala'a Chahwan, Richard 

作者机构：Univ Zurich Inst Expt Immunol Zurich Switzerland EVIIVE AG Zurich Switzerland 

出 版 物：《JOURNAL OF EXTRACELLULAR VESICLES》 (J. Extracell. Vesicles)

年 卷 期：2025年第14卷第1期

页      面：e70040页

核心收录：

基　　金：SNF [310030_212553, CRSK-3_190550, IZSEZ0_204655, IZSEZ0_218166] Novartis Foundation [22B140] Vontobel Stiftung UZH-STWF [F-41309-01-01] UZH-URPP (Translational Cancer Research) BioMedTech Entrepreneur Fellowship, BRIDGE-SNF [40B1-0_221565] GRS-Innobooster [GRS-069/23] SNSF-Chronoshub 320030E_215576 Swiss National Science Foundation (SNF) [310030_212553, IZSEZ0_204655] Funding Source: Swiss National Science Foundation (SNF) 

主　　题：antibody maturation extracellular vesicles intercellular epigenomic signalling non-coding RNA single particle analysis 

摘      要：B cell maturation is crucial for effective adaptive immunity. It requires a complex signalling network to mediate antibody diversification through mutagenesis. B cells also rely on queues from other cells within the germinal centre. Recently, a novel class of intercellular signals mediated by extracellular vesicles (EVs) has emerged. Studies have shown that B cell EV-mediated signalling is involved in immune response regulation and tumorigenesis. However, the mechanistic role of B cell EVs is not yet established. We herein study the biological properties and physiological function of B cell EVs during B cell maturation. We use emerging technologies to profile B cell EV surface marker signatures at the single particle level, molecular cargo and physiological roles in B cell maturation. EV ncRNA cargo, characterised by RNA-seq, identified an EV-mediated novel non-coding RNA (ncRNA) regulatory network for B cell maturation. We show that a previously uncharacterised micro-RNA (miR-5099) in combination with a set of long ncRNA are carried within B cell EVs and could contribute to antibody diversification. The physiological role of EVs in B cell maturation is investigated using EV blockade assays and complementation studies using diverse EV sources further confirmed the physiological role and mode of action of EVs in B cell maturation.