Tviblindi algorithm identifies branching developmental trajectories of human B‐cell development and describes abnormalities in RAG‐1 and WAS patients
Abstract: 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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European journal of immunology. - 54, 12 (2024) , 2451004, ISSN: 1521-4141
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Bakardjieva, Marina
Pelák, Ondřej
Wentink, Marjolein W.J
Glier, Hana
Novák, David
Stančíková, Jitka
Kužílková, Daniela
Mejstrikova, Ester
Janowska, Iga
Rizzi, Marta
Burg, Mirjam van der
Stuchly, Jan
Kalina, Tomas
- DOI
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10.1002/eji.202451004
- URN
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urn:nbn:de:bsz:25-freidok-2567851
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:23 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Bakardjieva, Marina
- Pelák, Ondřej
- Wentink, Marjolein W.J
- Glier, Hana
- Novák, David
- Stančíková, Jitka
- Kužílková, Daniela
- Mejstrikova, Ester
- Janowska, Iga
- Rizzi, Marta
- Burg, Mirjam van der
- Stuchly, Jan
- Kalina, Tomas
- Universität
Entstanden
- 2024
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