AKT activity orchestrates marginal zone B cell development in mice and humans
Cox, Eva Maria | El-Behi, Mohamed | Ries, Stefanie | Vogt, Johannes F. | Kohlhaas, Vivien | Michna, Thomas | Manfroi, Benoît | Al-Maarri, Mona | Wanke, Florian | Tirosh, Boaz | Pondarre, Corinne | Lezeau, Harry | Yogev, Nir | Mittenzwei, Romy | Descatoire, Marc | Weller, Sandra | Weill, Jean Claude | Reynaud, Claude Agnès | Boudinot, Pierre | Jouneau, Luc | Tenzer, Stefan | Distler, Ute | Rensing-Ehl, Anne | König, Christoph | Staniek, Julian | Rizzi, Marta | Magérus, Aude | Rieux-Laucat, Frédéric | Wunderlich, Frank Thomas | Hövelmeyer, Nadine | Fillatreau, Simon | Cohortes épidémiologiques en population (CONSTANCES) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité) | Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Centre Hospitalier Intercommunal de Créteil (CHIC) | Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) | Université Paris Cité (UPCité) | Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | ANR-18-CE17-0001; DRFZ; Institut Hospitalo-Universitaire Imagine, (ANR-10-IAHU-01, ANR-18-RHUS-0010); Regine von Ramin Laboratory; European Research Council, ERC, (647696); Deutsche Forschungsgemeinschaft, DFG, (318346496, HO4440/1-1, HO4440/1-2, SFB1292/2 TP20); Agence Nationale de la Recherche, ANR, (ANR-16-CE18-0007-01); Institut National de la Santé et de la Recherche Médicale, Inserm; Fondation pour la Recherche Médicale, FRM, (FRM EQU202103012670); Fritz Thyssen Stiftung, (AZ 10.13.2.173); Université Sorbonne Paris Cité, USPC, (B02, SFB1160) | ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018) | ANR-18-CE17-0001,ACTION,Cytopénies Auto-immunes: génétique et mécanismes physiopathologiques du syndrome d'Evans pédaitrique(2018) | European Project: 647696,H2020,ERC-2014-CoG,PREG-LAB(2016)
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Показать больше [+] Меньше [-]Английский. 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.
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