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Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients

M. Bakardjieva, O. Pelák, M. Wentink, H. Glier, D. Novák, J. Stančíková, D. Kužílková, E. Mejstříková, I. Janowska, M. Rizzi, M. van der Burg, J. Stuchlý, T. Kalina

. 2024 ; 54 (12) : e2451004. [pub] 20240905

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003283

Grantová podpora
23-05561S The Czech Science Foundation
23-07-00170 Czech Health Research Council
LX22NPO5102 European Union - Next Generation EU (Czech Recovery Plan) - Project National Cancer Research Institute
1S40421N FWO (Fonds Wetenschappelijk Onderzoek

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.

Citace poskytuje Crossref.org

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