c-Met and its ligand hepatocyte growth factor/scatter factor regulate mature B cell survival in a pathway induced by CD74.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Maya GordinIdit Shachar

Abstract

The signals regulating the survival of mature splenic B cells have become a major focus in recent studies of B cell immunology. Durable B cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism involved in mature B cell homeostasis, the hepatocyte growth factor/scatter factor (HGF)/c-Met pathway. We demonstrate that c-Met activation by HGF leads to a survival cascade, whereas its blockade results in induction of mature B cell death. Our results emphasize a unique and critical function for c-Met signaling in the previously described macrophage migration inhibitory factor/CD74-induced survival pathway. Macrophage migration inhibitory factor recruits c-Met to the CD74/CD44 complex and thereby enables the induction of a signaling cascade within the cell. This signal results in HGF secretion, which stimulates the survival of the mature B cell population in an autocrine manner. Thus, the CD74-HGF/c-Met axis defines a novel physiologic survival pathway in mature B cells, resulting in the control of the humoral immune response.

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Citations

Feb 26, 2013·Oncogene·I Binsky-EhrenreichI Shachar
Feb 13, 2015·Frontiers in Cellular Neuroscience·Phillip M UribeAllison B Coffin
Feb 13, 2018·Nature Reviews. Clinical Oncology·Kabir A Khan, Robert S Kerbel
Feb 24, 2015·Molecular and Cellular Biochemistry·Wenzheng XiaMeng Hou
Jan 18, 2018·Journal of Cellular Physiology·Mayrel Palestino-DominguezMaria Concepcion Gutierrez-Ruiz
Oct 3, 2018·The Journal of Clinical Investigation·Hadas LewinskyIdit Shachar
Jan 16, 2019·International Journal of Molecular Sciences·Paolo GiannoniDaniela de Totero
Jul 28, 2016·Oncogene·A MaromI Shachar
Oct 12, 2013·British Journal of Pharmacology·Sivan Cohen, Idit Shachar
Aug 16, 2019·Expert Opinion on Therapeutic Targets·Joshua B BilsborrowRichard Bucala
Apr 25, 2020·Muscle & Nerve·Aravindhan VeerapandiyanEmma Ciafaloni
Dec 6, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sivan CohenIdit Shachar
Jul 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jea-Hyun BaekThomas Hieronymus
Jul 31, 2012·FEBS Letters·Idit ShacharShirly Becker-Herman
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Jan 15, 2015·Biomedicines·Giuditta Viticchiè, Patricia A J Muller
Aug 4, 2018·Frontiers in Immunology·Fagui ZouJianbo Sun

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