期刊
CELL REPORTS
卷 24, 期 2, 页码 391-405出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.06.035
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资金
- DFG [TRR130, SFB1074, SFB1279]
- ERC advanced grant [694992]
- Egyptian Ministry of Higher Education (MoHE)
- German Academic Exchange Service (DAAD) within the German-Egyptian Research Long Term Scholarship Program (GERLS) [441, 91528030, 57030312]
- European Research Council (ERC) [694992] Funding Source: European Research Council (ERC)
Activation of phosphoinositide 3-kinase (PI3K) signaling plays a central role in regulating proliferation and survival of B cells. Here, we tested the hypothesis that B cell receptor (BCR)-mediated activation of PI3K induces the terminal differentiation factor Blimp-1 that interferes with proliferation and survival, thereby controlling the expansion of activated B cells. In fact, B-cell-specific inactivation of Pten, the negative regulator of PI3K signaling, leads to deregulated PI3K activity and elevated Blimp-1 expression. Combined deficiency for Pten and Blimp-1 results in abnormal expansion of B-1 B cells and splenomegaly. Interestingly, Blimp-1 also acts at early stages of B cell development to regulate B cell selection, as Blimp-1 deficiency results in an increased proportion of autoreactive B cells. Together, our data suggest that the combined requirement of deregulated PI3K signaling in addition to defective terminal differentiation represents the basis for proper selection and expansion of developing B cells.
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