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Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)\u2010stimulated B\u2010cell proliferation\/survival by suppressing mTOR\u2010mediated PP2A\u2010Erk1\/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF\u2010promoted B cell proliferation\/survival is also related to blocking hsBAFF\u2010stimulated phosphorylation of Akt, S6K1, and 4E\u2010BP1, as well as expression of survivin in normal and B\u2010lymphoid (Raji and Daudi) cells. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor or rictor enhanced rapamycin's suppression of hsBAFF\u2010induced survivin expression and proliferation\/viability in B cells. Also, PP242, an mTORC1\/2 kinase inhibitor, repressed survivin expression, and cell proliferation\/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Of interest, ectopic expression of constitutively active Akt (myr\u2010Akt) or constitutively active S6K1 (S6K1\u2010ca), or downregulation of 4E\u2010BP1 conferred resistance to rapamycin's attenuation of hsBAFF\u2010induced survivin expression and B\u2010cell proliferation\/viability, whereas overexpression of dominant negative Akt (dn\u2010Akt) or constitutively hypophosphorylated 4E\u2010BP1 (4EBP1\u20105A), or downregulation of S6K1, or co\u2010treatment with Akt inhibitor potentiated the inhibitory effects of rapamycin. The findings indicate that rapamycin attenuates excessive hsBAFF\u2010induced cell proliferation\/survival via blocking mTORC1\/2 signaling in normal and neoplastic B\u2010lymphoid cells. Our data underscore that rapamycin may be a potential agent for preventing excessive BAFF\u2010evoked aggressive B\u2010cell malignancies and autoimmune diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25913","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T17:53:56Z","timestamp":1489686836000},"page":"516-529","source":"Crossref","is-referenced-by-count":23,"title":["Rapamycin attenuates BAFF\u2010extended proliferation and survival via disruption of mTORC1\/2 signaling in normal and neoplastic B\u2010lymphoid cells"],"prefix":"10.1002","volume":"233","author":[{"given":"Qingyu","family":"Zeng","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences Nanjing Normal University Nanjing PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Qin","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and 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