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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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
Subjects:
Online Access:https://doi.org/10.1002/jev2.70040
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author Kevin Ho Wai Yim
Ala'a Al Hrout
Richard Chahwan
author_facet Kevin Ho Wai Yim
Ala'a Al Hrout
Richard Chahwan
author_sort Kevin Ho Wai Yim
collection DOAJ
description 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.
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spelling doaj-art-4ad717de87a14dd59bb15450a0bdec312025-08-20T02:41:52ZengWileyJournal of Extracellular Vesicles2001-30782025-01-01141n/an/a10.1002/jev2.70040Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell MaturationKevin Ho Wai Yim0Ala'a Al Hrout1Richard Chahwan2Institute of Experimental Immunology University of Zurich Zurich SwitzerlandInstitute of Experimental Immunology University of Zurich Zurich SwitzerlandInstitute of Experimental Immunology University of Zurich Zurich SwitzerlandABSTRACT 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.https://doi.org/10.1002/jev2.70040antibody maturationextracellular vesiclesintercellular epigenomic signallingnon‐coding RNAsingle particle analysis
spellingShingle Kevin Ho Wai Yim
Ala'a Al Hrout
Richard Chahwan
Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
Journal of Extracellular Vesicles
antibody maturation
extracellular vesicles
intercellular epigenomic signalling
non‐coding RNA
single particle analysis
title Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
title_full Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
title_fullStr Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
title_full_unstemmed Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
title_short Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation
title_sort intercellular epigenomic signalling via extracellular vesicles during b cell maturation
topic antibody maturation
extracellular vesicles
intercellular epigenomic signalling
non‐coding RNA
single particle analysis
url https://doi.org/10.1002/jev2.70040
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AT alaaalhrout intercellularepigenomicsignallingviaextracellularvesiclesduringbcellmaturation
AT richardchahwan intercellularepigenomicsignallingviaextracellularvesiclesduringbcellmaturation