mTOR intersects antibody-inducing signals from TACI in marginal zone B cells
Authors: Michael Hahne
Daniel Segura-Garzón
Laura Comerma
Josep Lloreta
Jordi Sintes
Manel Juan
Alessandra Ciociola
Eric Meffre
Bing He
Beverly A Mock
Marta Crespo
Sergi Serrano
Giuliana Magri
Irene Puga
Linda Cassis
Jordi Yagüe
Marc Pybus
Juan Ignacio Aróstegui
Yolanda Garcia-Carmona
Maurizio Gentile
Sabrina Bascones
David Lligé
Charlotte Cunningham-Rundles
Emilie K Grasset
Julio Pascual
Cindy Gutzeit
Wendy DuBois
Anna Mensa
Andrea Cerutti
Shuling Zhang
Journal: Nature Communications (2017)
Discipline: Multidisciplinary
Keywords: mTOR; immunometabolic reconfiguration; marginal zone B cells; TLR; TACI
Affiliations: Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, 08003, Spain. ., Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, 08003, Spain., Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Department of Medicine and Pediatrics, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Department of Medicine, Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institutet, Stockholm, 171 76, Sweden., Department of Nephrology, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, 08003, Spain., Immunology Service, Hospital Clínic of Barcelona, Barcelona, 08036, Spain., Department of Pathology, Hospital del Mar, Barcelona, 08003, Spain., Universitat Pompeu Fabra, Barcelona, 08003, Spain., Department of Immunobiology, Yale University, New Haven, CT, 06511, USA., Molecular Genetics Institute of Montpellier, Montpellier, 34293, France., Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. ., Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, 08003, Spain. .

Abstract:  Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB. Disruption of TACI-mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-κB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs. 

Retracted: No

PubPeer comments:
 Fig 7B.  Comparison of caspase-9 activities of LS-174T cell line in the three groups . ![file] The resolution is nothing to celebrate, but it is still good enough to see the high similarity between the three panels and corresponding panels in Fig 4A of [Zhou et al (2018)] , and other manifestations adduced in that thread: ![] , 
 Figs 2C, 4C, 10D. ![file] The stylised nature of the Western Blots in this paper are suggestive of a papermill provenance. Other examples are tabulated in a spreadsheet. https: docs.google.com spreadsheets d 1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY edit?usp=sharing Compare, for instance, the loading control from 7B of [Zhou et al (2018)] . ![file] , 
 Retracted [30 June 2021] . ------------------------------ The above article, published online on 19 May 2017 in Wiley Online Library has been retracted by agreement between the the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,