The p110delta subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells.
PI3K (phosphoinositide 3-kinase) I(A) family members contain a regulatory subunit and a catalytic subunit. The p110delta catalytic subunit is expressed predominantly in haematopoietic cells. There, among other functions, it regulates antigen receptor-mediated responses. Using mice deficient in the p110delta 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), p110delta(-/-) 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 p110delta(-/-) B cells. They showed normal extracellular-signal-regulated kinase phosphorylation, but anti-RP105-induced protein kinase B, IkappaB (inhibitor of nuclear factor kappaB) and c-Jun N-terminal kinase activation was severely reduced. This demonstrates that the p110delta 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.
Hebeis
B J
BJ
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK. barbara.j.hebeis@gsk.com
Vigorito
E
E
Turner
M
M
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D051940:B7-2 Antigen; D020134:Catalytic Domain; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases; D004789:Enzyme Activation; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D015854:Up-Regulation
D015703:Antigens, CD; D051940:B7-2 Antigen; D058534:Class I Phosphatidylinositol 3-Kinases; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D015375:Receptors, Interleukin-2; C497965:Cd86 protein, mouse; C421683:Pik3cd protein, mouse