BAFF inhibits autophagy promoting cell proliferation and survival by activating Ca2+ -CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells

Cellular Signalling
Xiaoqing DongLong Chen

Abstract

B cell activating factor from the TNF family (BAFF) is implicated in not only the physiology of normal B cells, but also the pathophysiology of aggressive B cells related to malignant and autoimmune diseases. Autophagy plays a crucial role in balancing the beneficial and detrimental effects of immunity and inflammation. However, little is known about whether and how excessive BAFF mediates autophagy contributing to B-cell proliferation and survival. Here, we show that excessive human soluble BAFF (hsBAFF) inhibited autophagy with a concomitant reduction of LC3-II in normal and B-lymphoid (Raji) cells. Knockdown of LC3 not only potentiated hsBAFF inhibition of autophagy, but also attenuated hsBAFF activation of Akt/mTOR pathway, thereby diminishing hsBAFF-induced B-cell proliferation/viability. Further, we found that hsBAFF inhibition of autophagy was Akt/mTOR-dependent. This is supported by the findings that hsBAFF increased mTORC1-mediated phosphorylation of ULK1 (Ser757); Akt inhibitor X, mTORC1 inhibitor rapamycin, mTORC1/2 inhibitor PP242, expression of dominant negative Akt, or knockdown of mTOR attenuated hsBAFF-induced phosphorylation of ULK1, decrease of LC3-II level, and increase of cell proliferation/viability. Chelat...Continue Reading

Citations

Aug 1, 2020·Frontiers in Immunology·Jacob D PainterOmid Akbari
Aug 30, 2019·International Journal of Molecular Sciences·Silvia SorrentinoBianca Maria Scicchitano
Feb 23, 2021·Frontiers in Immunology·Erik M MatsonPaul J Maglione
Mar 6, 2021·Journal of Cancer Research and Clinical Oncology·Zenan Lin, Daniela Süsskind
Apr 19, 2021·Cancer Cell International·Guangchao LiShuang Liu
Jun 27, 2021·Current Opinion in Immunology·Ellen McAllister, Julia Jellusova
Oct 10, 2021·Oncogene·Fedor BerditchevskiPaul G Murray

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