Yim Kevin Ho Wai, Al Hrout Ala'a, Chahwan Richard
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
EVIIVE AG, Zurich, Switzerland.
J Extracell Vesicles. 2025 Jan;14(1):e70040. doi: 10.1002/jev2.70040.
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.
B细胞成熟对于有效的适应性免疫至关重要。它需要一个复杂的信号网络来通过诱变介导抗体多样化。B细胞还依赖生发中心内其他细胞发出的信号。最近，一类由细胞外囊泡（EVs）介导的新型细胞间信号出现了。研究表明，B细胞EV介导的信号传导参与免疫反应调节和肿瘤发生。然而，B细胞EVs的机制作用尚未确定。我们在此研究B细胞成熟过程中B细胞EVs的生物学特性和生理功能。我们使用新兴技术在单颗粒水平分析B细胞EV表面标志物特征、分子货物以及在B细胞成熟中的生理作用。通过RNA测序表征的EV非编码RNA货物，确定了一个由EV介导的用于B细胞成熟的新型非编码RNA（ncRNA）调控网络。我们表明，一种以前未被表征的微小RNA（miR-5099）与一组长链ncRNA一起存在于B细胞EVs中，并可能有助于抗体多样化。使用EV阻断试验研究了EVs在B细胞成熟中的生理作用，使用不同EV来源的互补研究进一步证实了EVs在B细胞成熟中的生理作用和作用模式。
