Requirement for Phosphoinositide 3-kinase P110delta Signaling in B Cell Antigen Receptor-mediated Antigen Presentation.
From: Department of Immunology, University of Manitoba, Winnipeg, Canada.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 4
- Pages: 2328-35
- Medium: Print
- Language: English
- Citation (JAMA): Al-Alwan Monther M, Okkenhaug Klaus, Vanhaesebroeck Bart, et al. Requirement for Phosphoinositide 3-kinase P110delta Signaling in B Cell Antigen Receptor-mediated Antigen Presentation.. J. Immunol. Feb 2007;178:2328-35
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.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Animals, Antigen Presentation, B-Lymphocytes, Cells, Cultured, Endosomes, Lymphocyte Activation, Lysosomes, Mice, Mice, Mutant Strains, Proto-Oncogene Proteins c-bcr, Signal Transduction, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 17277138
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