Marina Bakardjieva, Ondřej Pelák, Marjolein Wentink, Hana Glier, David Novák, Jitka Stančíková, Daniela Kužílková, Ester Mejstříková, Iga Janowska, Marta Rizzi, Mirjam van der Burg, Jan Stuchlý, Tomáš Kalina
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引用次数: 0
摘要
详细了解人类 B 细胞的发育过程对于正确解释先天性免疫错误和恶性疾病至关重要。我们有兴趣了解发育过程中蛋白质表达变化的动力学,同时也有兴趣正确解释主要的和可能替代的发育轨迹。我们研究了健康人的人体样本,旨在描述所有 B 细胞的发育轨迹。我们验证了 30 个参数的质谱面板,并展示了 B 细胞发育阶段 "vaevictis "可视化的实用性。我们使用轨迹推断工具 "tviblindi "详尽描述了数据中发现的所有发育终点的所有轨迹。我们以天然效应 B 细胞为重点,展示了核因子(PAX-5、TdT、Ki-67、Bcl-2)、细胞因子和趋化因子受体(CD127、CXCR4、CXCR5)与典型 B 细胞发育阶段标志物的表达动态。我们观察到记忆发育的分支,其中滤泡记忆的形成以 CD73 的表达为标志。最后,我们分析了两个原发性免疫缺陷患者因 RAG-1 和 Wiskott-Aldrich 综合征基因突变而导致 B 细胞发育异常的病例。总之,我们开发、验证并展示了一套用于研究骨髓区 B 细胞发育的综合工具。
Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients
Detailed knowledge of human B-cell development is crucial for the proper interpretation of inborn errors of immunity and malignant diseases. It is of interest to understand the kinetics of protein expression changes during development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human samples from healthy individuals with the aim of describing all B-cell developmental trajectories. We validated a 30-parameter mass cytometry panel and demonstrated the utility of “vaevictis” visualization of B-cell developmental stages. We used the trajectory inference tool “tviblindi” to exhaustively describe all trajectories leading to all developmental ends discovered in the data. Focusing on Natural Effector B cells, we demonstrated the dynamics of expression of nuclear factors (PAX-5, TdT, Ki-67, Bcl-2), cytokine and chemokine receptors (CD127, CXCR4, CXCR5) in relation to the canonical B-cell developmental stage markers. We observed branching of the memory development, where follicular memory formation was marked by CD73 expression. Lastly, we performed an analysis of two example cases of abnormal B-cell development caused by mutations in RAG-1 and Wiskott–Aldrich syndrome gene in patients with primary immunodeficiency. In conclusion, we developed, validated, and presented a comprehensive set of tools for the investigation of B-cell development in the bone marrow compartment.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.