[en] 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.
Yim, Kevin Ho Wai; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland ; EVIIVE AG, Zurich, Switzerland
Al Hrout, Ala'a ; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
CHAHWAN, Richard ; University of Luxembourg ; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland ; EVIIVE AG, Zurich, Switzerland
External co-authors :
yes
Language :
English
Title :
Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation.
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung Vontobel-Stiftung Novartis Foundation
Funding text :
We thank the Exeter Sequencing facility particularly Paul O'Neil and Karen Moore for help and advice. Christian Hacker and UZH microscopy facility for TEM support and advice. Bogdan Mateescu for discussions. Profs Matthew Scharff and Christian M\u00FCnz for critical reading of the manuscript. R.C. is supported by SNF (310030_212553; 320030E_215576, CRSK\u20103_190550; IZSEZ0_204655; IZSEZ0_218166), Novartis Foundation (22B140), Vontobel Stiftung (41309), UZH\u2010STWF (F\u201041309\u201001\u201001) and the UZH\u2010URPP (Translational Cancer Research). K.Y. is supported by a BioMedTech Entrepreneur Fellowship, BRIDGE\u2010SNF (40B1\u20100_221565) and GRS\u2010Innobooster (GRS\u2010069/23). Funding for open access charge: SNSF\u2010Chronoshub.R.C. is supported by\u00A0SNF\u00A0(310030_212553; 320030E_215576, CRSK-3_190550; IZSEZ0_204655; IZSEZ0_218166),\u00A0Novartis Foundation\u00A0(22B140),\u00A0Vontobel\u00A0Stiftung (41309), UZH-STWF\u00A0(F-41309-01-01) and the UZH-URPP (Translational Cancer Research). K.Y. is supported by a BioMedTech Entrepreneur Fellowship, BRIDGE-SNF (40B1-0_221565) and GRS-Innobooster (GRS-069/23). Funding for open access charge: SNSF-Chronoshub.We thank the Exeter Sequencing facility particularly Paul O'Neil and Karen Moore for help and advice. Christian Hacker and UZH microscopy facility for TEM support and advice. Bogdan Mateescu for discussions. Profs Matthew Scharff and Christian M\u00FCnz for critical reading of the manuscript. R.C. is supported by\u00A0SNF\u00A0(310030_212553; 320030E_215576, CRSK-3_190550; IZSEZ0_204655; IZSEZ0_218166),\u00A0Novartis Foundation\u00A0(22B140),\u00A0Vontobel\u00A0Stiftung (41309), UZH-STWF\u00A0(F-41309-01-01) and the UZH-URPP (Translational Cancer Research). K.Y. is supported by a BioMedTech Entrepreneur Fellowship, BRIDGE-SNF (40B1-0_221565) and GRS-Innobooster (GRS-069/23). Funding for open access charge: SNSF-Chronoshub.: R.C. is supported by SNF (310030_212553; 320030E_215576, CRSK\u20103_190550; IZSEZ0_204655; IZSEZ0_218166), Novartis Foundation (22B140), Vontobel Stiftung (41309), UZH\u2010STWF (F\u201041309\u201001\u201001) and the UZH\u2010URPP (Translational Cancer Research). K.Y. is supported by a BioMedTech Entrepreneur Fellowship, BRIDGE\u2010SNF (40B1\u20100_221565) and GRS\u2010Innobooster (GRS\u2010069/23). Funding for open access charge: SNSF\u2010Chronoshub. Funding
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