Cell Reports (Apr 2023)
AKT activity orchestrates marginal zone B cell development in mice and humans
- Eva-Maria Cox,
- Mohamed El-Behi,
- Stefanie Ries,
- Johannes F. Vogt,
- Vivien Kohlhaas,
- Thomas Michna,
- Benoît Manfroi,
- Mona Al-Maarri,
- Florian Wanke,
- Boaz Tirosh,
- Corinne Pondarre,
- Harry Lezeau,
- Nir Yogev,
- Romy Mittenzwei,
- Marc Descatoire,
- Sandra Weller,
- Jean-Claude Weill,
- Claude-Agnès Reynaud,
- Pierre Boudinot,
- Luc Jouneau,
- Stefan Tenzer,
- Ute Distler,
- Anne Rensing-Ehl,
- Christoph König,
- Julian Staniek,
- Marta Rizzi,
- Aude Magérus,
- Frederic Rieux-Laucat,
- F. Thomas Wunderlich,
- Nadine Hövelmeyer,
- Simon Fillatreau
Affiliations
- Eva-Maria Cox
- Institute for Molecular Medicine Mainz, University Hospital of Mainz, 55131 Mainz, Germany
- Mohamed El-Behi
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France
- Stefanie Ries
- Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, 10117 Berlin, Germany
- Johannes F. Vogt
- Institute for Molecular Medicine Mainz, University Hospital of Mainz, 55131 Mainz, Germany
- Vivien Kohlhaas
- Max Planck Institute for Metabolism Research Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP) Cologne, 50931 Cologne, Germany
- Thomas Michna
- Institute for Immunology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
- Benoît Manfroi
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France
- Mona Al-Maarri
- Max Planck Institute for Metabolism Research Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP) Cologne, 50931 Cologne, Germany
- Florian Wanke
- Institute for Molecular Medicine Mainz, University Hospital of Mainz, 55131 Mainz, Germany
- Boaz Tirosh
- The Hebrew University of Jerusalem, Institute for Drug Research, Jerusalem, Israel
- Corinne Pondarre
- Service de Pédiatrie Générale, Centre de Référence de la Drépanocytose, Centre Intercommunal de Créteil, Créteil, France; Inserm U955, Université Paris XII, Créteil, France
- Harry Lezeau
- Service de Pédiatrie Générale, Centre de Référence de la Drépanocytose, Centre Intercommunal de Créteil, Créteil, France; Inserm U955, Université Paris XII, Créteil, France
- Nir Yogev
- Faculty of Medicine, Department of Dermatology, University of Cologne, 50931 Cologne, Germany
- Romy Mittenzwei
- Institute for Molecular Medicine Mainz, University Hospital of Mainz, 55131 Mainz, Germany
- Marc Descatoire
- Laboratory of Immune Inherited Disorders, Department of Immunology and Allergology Lausanne Hospital CHUV, Lausanne, Switzerland
- Sandra Weller
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France
- Jean-Claude Weill
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France
- Claude-Agnès Reynaud
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France
- Pierre Boudinot
- Université Paris-Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France
- Luc Jouneau
- Université Paris-Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France
- Stefan Tenzer
- Institute for Immunology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany; Research Centre for Immunotherapy (FZI), University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz), Mainz, Germany
- Ute Distler
- Institute for Immunology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
- Anne Rensing-Ehl
- Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Christoph König
- Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; University of Freiburg, Faculty of Biology, Schaenzlestrasse 1, 79104 Freiburg, Germany
- Julian Staniek
- Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Marta Rizzi
- Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Aude Magérus
- Université Paris Cité, Institut Imagine, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France
- Frederic Rieux-Laucat
- Université Paris Cité, Institut Imagine, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France
- F. Thomas Wunderlich
- Max Planck Institute for Metabolism Research Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP) Cologne, 50931 Cologne, Germany
- Nadine Hövelmeyer
- Institute for Molecular Medicine Mainz, University Hospital of Mainz, 55131 Mainz, Germany; Research Centre for Immunotherapy (FZI), University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany; Corresponding author
- Simon Fillatreau
- Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, 156-160, rue de Vaugirard, 75015 Paris, France; Université de Paris Cité, Paris Descartes, Faculté de Médecine, Paris, France; AP-HP, Hôpital Necker Enfants Malades, Paris, France; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 4
p. 112378
Abstract
Summary: The signals controlling marginal zone (MZ) and follicular (FO) B cell development remain incompletely understood. Here, we show that AKT orchestrates MZ B cell formation in mice and humans. Genetic models that increase AKT signaling in B cells or abolish its impact on FoxO transcription factors highlight the AKT-FoxO axis as an on-off switch for MZ B cell formation in mice. In humans, splenic immunoglobulin (Ig) D+CD27+ B cells, proposed as an MZ B cell equivalent, display higher AKT signaling than naive IgD+CD27− and memory IgD−CD27+ B cells and develop in an AKT-dependent manner from their precursors in vitro, underlining the conservation of this developmental pathway. Consistently, CD148 is identified as a receptor indicative of the level of AKT signaling in B cells, expressed at a higher level in MZ B cells than FO B cells in mice as well as humans.
