First Author | Al-Alwan MM | Year | 2007 |
Journal | J Immunol | Volume | 178 |
Issue | 4 | Pages | 2328-35 |
PubMed ID | 17277138 | Mgi Jnum | J:143983 |
Mgi Id | MGI:3829557 | Doi | 10.4049/jimmunol.178.4.2328 |
Citation | Al-Alwan MM, et al. (2007) Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation. J Immunol 178(4):2328-35 |
abstractText | 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. |