Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation

ABSTRACT 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...

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Bibliographic Details
Main Authors: Kevin Ho Wai Yim, Ala'a Al Hrout, Richard Chahwan
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Extracellular Vesicles
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Online Access:https://doi.org/10.1002/jev2.70040
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Summary:ABSTRACT 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.
ISSN:2001-3078