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J Immunol. 2007 Feb 15;178(4):2328-35.

Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation.

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  • 1Department of Immunology, University of Manitoba, Winnipeg, Canada.

Abstract

The BCR serves to both signal cellular activation and enhance uptake and presentation of Ags by B cells; however, the intracellular signaling mechanisms linking the BCR to Ag presentation functions have been controversial. PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110delta isoform playing a critical role in BCR signaling. In this study, we used pharmacological and genetic approaches to evaluate the role of p110delta signaling in Ag presentation by primary B lymphocytes. It was found that activation of allogeneic T cells is significantly reduced when B cells are pretreated with global PI3K inhibitors, but was intact when p110delta signaling was specifically inactivated. In contrast, inactivation of p110delta significantly impaired the ability of B cells to activate T cells in a BCR-mediated Ag uptake and presentation model. Prestimulation of p110delta-inactivated B cells with anti-CD40 or LPS could not rescue their BCR-mediated Ag presentation ability to normal levels. p110delta signaling was required for efficient presentation of either anti-Ig or protein Ag via a lysozyme-specific BCR. p110delta-inactivated B cells were able to internalize Ag normally, and no defects in association of Ag with lysosome-associated membrane protein 1(+) late endosomes were observed; however, these cells were less effective in forming polarized conjugates with Ag-specific T cells. Our data demonstrate a role for p110delta signaling in B cell Ag presentation function, implicating 3-phosphoinositides and their targets in the latter stages of this process.

PMID:
17277138
[PubMed - indexed for MEDLINE]
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