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 Pondarré, 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, Frédéric Rieux‐Laucat, F. Thomas Wunderlich, Nadine Hövelmeyer, Simon Fillatreau
Abstract
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.