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Mammalian target of rapamycin complex 1 signalling is essential for germinal centre reaction
Author(s) -
Li Bingshou,
Li Zhirong,
Wang Pengcheng,
Huang Qizhao,
Xu Lifan,
He Ran,
Ye Lilin,
Bai Qiang
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12767
Subject(s) - signalling , biology , signalling pathways , microbiology and biotechnology , computational biology , chemistry , signal transduction
Summary The mammalian target of rapamycin ( mTOR ) is a serine‐threonine kinase that has been shown to be essential for the differentiation and function of various immune cells. Earlier in vitro studies showed that mTOR signalling regulates B‐cell biology by supporting their activation and proliferation. However, how mTOR signalling temporally regulates in vivo germinal centre B ( GCB ) cell development and differentiation into short‐lived plasma cells, long‐lived plasma cells and memory cells is still not well understood. In this study, we used a combined conditional/inducible knock‐out system to investigate the temporal regulation of mTOR complex 1 ( mTORC 1) in the GCB cell response to acute lymphocytic choriomeningitis virus infection by deleting Raptor, a main component of mTORC 1, specifically in B cells in pre‐ and late GC phase. Early Raptor deficiency strongly inhibited GCB cell proliferation and differentiation and plasma cell differentiation. Nevertheless, late GC Raptor deficiency caused only decreases in the size of memory B cells and long‐lived plasma cells through poor maintenance of GCB cells, but it did not change their differentiation. Collectively, our data revealed that mTORC 1 signalling supports GCB cell responses at both early and late GC phases during viral infection but does not regulate GCB cell differentiation into memory B cells and plasma cells at the late GC stage.