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International Immunology, Vol. 13, No. 6, 807-816, June 2001
© 2001 Japanese Society for Immunology

Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-{kappa}B activation in primary B cells

Heather Bone and Neil A. Williams

Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK

Correspondence to: N. A. Williams

The NF-{kappa}B/Rel transcription factors play an important role in the expression of genes involved in B cell development, differentiation and function. Nuclear NF-{kappa}B is induced in B cells by engagement of either the BCR or CD40 or by stimulation with lipopolysaccharide (LPS). Despite the importance of NF-{kappa}B to B cell function, little is known about the signaling pathways leading to NF-{kappa}B activation. In this report we address the role of phosphoinositide 3'-kinase (PI 3-kinase) in BCR- and LPS-induced NF-{kappa}B activation using populations of primary murine resting B cells. Using the specific pharmacological inhibitors of PI 3-kinase, Wortmannin and LY294002, we demonstrate that PI 3-kinase activity is vital for BCR-induced NF-{kappa}B DNA-binding activity. Furthermore, we show that this is achieved via protein kinase C-dependent degradation of I{kappa}B{alpha}. Similar analyses reveal that PI 3-kinase is also critical in triggering NF-{kappa}B DNA-binding activity and I{kappa}B{alpha} degradation following LPS stimulation. Interestingly, a PKC inhibitor which blocked the BCR-induced I{kappa}B{alpha} degradation had no effect on the degradation of I{kappa}B{alpha} after LPS stimulation. Taken together, our results indicate the involvement of PI 3-kinase in at least two distinct signaling pathways leading to activation of NF-{kappa}B in B cells.

Keywords: BCR, lipopolysaccharide, protein kinase B, protein kinase C

Transmitting editor: M. Neuberger


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