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

doi:10.1016/j.celrep.2023.112378

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 JouneauStefan Tenzer, Ute Distler, Anne Rensing-Ehl, Christoph König, Julian Staniek, Marta Rizzi, Aude Magérus, Frederic Rieux-Laucat, F. Thomas Wunderlich, Nadine Hövelmeyer, Simon Fillatreau

School of Pharmacy

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	112378
Pages (from-to)	1-24
Journal	Cell Reports
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2023.112378
State	Published - 25 Apr 2023

Keywords

AKT
ALPS
B cells
CD148
CP: Developmental biology
CP: Immunology
FoxO1
NOTCH2
marginal zone B cells

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2023.112378

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Cox, E. M., El-Behi, M., Ries, S., Vogt, J. F., Kohlhaas, V., Michna, T., Manfroi, B., Al-Maarri, M., Wanke, F., Tirosh, B., Pondarre, C., Lezeau, H., Yogev, N., Mittenzwei, R., Descatoire, M., Weller, S., Weill, J. C., Reynaud, C. A., Boudinot, P., ... Fillatreau, S. (2023). AKT activity orchestrates marginal zone B cell development in mice and humans. Cell Reports, 42(4), 1-24. Article 112378. https://doi.org/10.1016/j.celrep.2023.112378

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title = "AKT activity orchestrates marginal zone B cell development in mice and humans",

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.",

keywords = "AKT, ALPS, B cells, CD148, CP: Developmental biology, CP: Immunology, FoxO1, NOTCH2, marginal zone B cells",

author = "Cox, \{Eva Maria\} and Mohamed El-Behi and Stefanie Ries and Vogt, \{Johannes F.\} and Vivien Kohlhaas and Thomas Michna and Beno{\^i}t Manfroi and Mona Al-Maarri and Florian Wanke and Boaz Tirosh and Corinne Pondarre and Harry Lezeau and Nir Yogev and Romy Mittenzwei and Marc Descatoire and Sandra Weller and Weill, \{Jean Claude\} and Reynaud, \{Claude Agn{\`e}s\} and Pierre Boudinot and Luc Jouneau and Stefan Tenzer and Ute Distler and Anne Rensing-Ehl and Christoph K{\"o}nig and Julian Staniek and Marta Rizzi and Aude Mag{\'e}rus and Frederic Rieux-Laucat and Wunderlich, \{F. Thomas\} and Nadine H{\"o}velmeyer and Simon Fillatreau",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = apr,

day = "25",

doi = "10.1016/j.celrep.2023.112378",

language = "الإنجليزيّة",

volume = "42",

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Cox, EM, El-Behi, M, Ries, S, Vogt, JF, Kohlhaas, V, Michna, T, Manfroi, B, Al-Maarri, M, Wanke, F, Tirosh, B, Pondarre, C, Lezeau, H, Yogev, N, Mittenzwei, R, Descatoire, M, Weller, S, Weill, JC, Reynaud, CA, Boudinot, P, Jouneau, L, Tenzer, S, Distler, U, Rensing-Ehl, A, König, C, Staniek, J, Rizzi, M, Magérus, A, Rieux-Laucat, F, Wunderlich, FT, Hövelmeyer, N & Fillatreau, S 2023, 'AKT activity orchestrates marginal zone B cell development in mice and humans', Cell Reports, vol. 42, no. 4, 112378, pp. 1-24. https://doi.org/10.1016/j.celrep.2023.112378

TY - JOUR

T1 - AKT activity orchestrates marginal zone B cell development in mice and humans

AU - Cox, Eva Maria

AU - El-Behi, Mohamed

AU - Ries, Stefanie

AU - Vogt, Johannes F.

AU - Kohlhaas, Vivien

AU - Michna, Thomas

AU - Manfroi, Benoît

AU - Al-Maarri, Mona

AU - Wanke, Florian

AU - Tirosh, Boaz

AU - Pondarre, Corinne

AU - Lezeau, Harry

AU - Yogev, Nir

AU - Mittenzwei, Romy

AU - Descatoire, Marc

AU - Weller, Sandra

AU - Weill, Jean Claude

AU - Reynaud, Claude Agnès

AU - Boudinot, Pierre

AU - Jouneau, Luc

AU - Tenzer, Stefan

AU - Distler, Ute

AU - Rensing-Ehl, Anne

AU - König, Christoph

AU - Staniek, Julian

AU - Rizzi, Marta

AU - Magérus, Aude

AU - Rieux-Laucat, Frederic

AU - Wunderlich, F. Thomas

AU - Hövelmeyer, Nadine

AU - Fillatreau, Simon

PY - 2023/4/25

Y1 - 2023/4/25

N2 - 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.

AB - 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.

KW - AKT

KW - ALPS

KW - B cells

KW - CD148

KW - CP: Developmental biology

KW - CP: Immunology

KW - FoxO1

KW - NOTCH2

KW - marginal zone B cells

UR - http://www.scopus.com/inward/record.url?scp=85153538050&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.112378

DO - 10.1016/j.celrep.2023.112378

M3 - مقالة

C2 - 37060566

SN - 2211-1247

VL - 42

SP - 1

EP - 24

JO - Cell Reports

JF - Cell Reports

IS - 4

M1 - 112378

ER -

AKT activity orchestrates marginal zone B cell development in mice and humans

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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