PI3K (phosphoinositide 3-kinase) IA family members contain a regulatory subunit and a catalytic subunit. The p110δ catalytic subunit is expressed predominantly in haematopoietic cells. There, among other functions, it regulates antigen receptor-mediated responses. Using mice deficient in the p110δ subunit of PI3K, we investigated the role of this subunit in LPS (lipopolysaccharide)-induced B cell responses, which are mediated by Toll-like receptor 4 and RP105. After injection of DNP-LPS (where DNP stands for 2,4-dinitrophenol), p110δ−/− mice produced reduced levels of DNP-specific IgM and IgG when compared with wild-type mice. In vitro, the proliferation and up-regulation of surface activation markers such as CD86 and CD25 induced by LPS and an antibody against RP105 were decreased. We analysed the activation state of key components of the LPS pathway in B cells to determine whether there was a defect in signalling in p110δ−/− B cells. They showed normal extracellular-signal-regulated kinase phosphorylation, but anti-RP105-induced protein kinase B, IκB (inhibitor of nuclear factor κB) and c-Jun N-terminal kinase activation was severely reduced. This demonstrates that the p110δ subunit of PI3K is involved in the LPS response in B cells and may represent a link between the innate and the adaptive immune system.
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Conference Article|
October 26 2004
The p110δ subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells
B.J. Hebeis;
B.J. Hebeis
1
1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, U.K.
1To whom correspondence should be addressed (email barbara.j.hebeis@gsk.com).
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E. Vigorito;
E. Vigorito
1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, U.K.
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M. Turner
M. Turner
1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, U.K.
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Publisher: Portland Press Ltd
Received:
July 09 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 The Biochemical Society
2004
Biochem Soc Trans (2004) 32 (5): 789–791.
Article history
Received:
July 09 2004
Citation
B.J. Hebeis, E. Vigorito, M. Turner; The p110δ subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells. Biochem Soc Trans 1 November 2004; 32 (5): 789–791. doi: https://doi.org/10.1042/BST0320789
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