Tviblindi algorithm identifies branching developmental trajectories of human B cell development
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Detailed knowledge of the human B-cell development is crucial for proper interpretation of inborn errors of immunity and for malignant diseases. It is of interest to understand the kinetics of protein expression changes during the B cell development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human bone marrow and peripheral blood samples from healthy individuals with the aim to describe all B-cell developmental trajectories across the two tissues. We validated a 30-parameter mass cytometry panel and demonstrated the utility of “ vaevictis ” visualization of B-cell developmental stages. We used our recently developed 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 (CD34, CD10, sIgM, IgD, CD20, CD27). Lastly, we performed analysis of the expression changes related to developmental branching points (Natural Effector versus Switched Memory B cells, marked by up-regulation of CD73). In conclusion, we developed, validated and presented a comprehensive set of tools for investigation of B-cell development.
Authors 12
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Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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Charles University · University Hospital in Motol
Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
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Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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Affiliation as printed
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
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Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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Charles University · Ghent University · VIB-UGent Center for Inflammation Research
Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
Data Mining and Modeling for Biomedicine, Center for Inflammation Research, VIB-UGent, Technologiepark-Zwijnaarde 71, Ghent, Belgium
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Krijgslaan 281-S9, Ghent, Belgium
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Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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Charles University · University Hospital in Motol
Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
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University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Department of Rheumatology and Clinical Immunology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany
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University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Department of Rheumatology and Clinical Immunology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany
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Leiden University Medical Center
Affiliation as printed
Department of Pediatrics, Laboratory for Pediatric Immmunology, Leiden University Medical Center, Leiden, Netherlands
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Tomáš Kalina corresponding
Charles University · University Hospital in Motol
Affiliation as printed
CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
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