1. AKT activity orchestrates marginal zone B cell development in mice and humans
- Author
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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, and Simon Fillatreau
- Subjects
CP: Immunology ,CP: Developmental biology ,Biology (General) ,QH301-705.5 - 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.
- Published
- 2023
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