CD86 stimulation on a B cell activates the phosphatidylinositol 3-kinase/Akt and phospholipase C gamma 2/protein kinase C alpha beta signaling pathways

• Published in: Journal of Immunology 2006-06, Vol.176 (11), p.6727-6735
• Main Authors: Kin, Nicholas W, Sanders, Virginia M
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; B7-2 Antigen - genetics; B7-2 Antigen - metabolism; B7-2 Antigen - physiology; Cell Line, Tumor; Enhancer Elements, Genetic; Enzyme Activation - genetics; Enzyme Activation - immunology; Female; I-kappa B Kinase - metabolism; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Isoenzymes - metabolism; Isoenzymes - physiology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Knockout; NF-kappa B - genetics; NF-kappa B - metabolism; Octamer Transcription Factor-2 - genetics; Octamer Transcription Factor-2 - metabolism; Phosphatidylinositol 3-Kinases - deficiency; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phospholipase C gamma - metabolism; Phospholipase C gamma - physiology; Protein Kinase C - metabolism; Protein Kinase C - physiology; Protein Kinase C beta; Protein Kinase C-alpha - metabolism; Protein Kinase C-alpha - physiology; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - genetics; Signal Transduction - immunology
• ISSN: 0022-1767; 1365-2567
• DOI: 10.4049/jimmunol.176.11.6727

Stimulation of CD86 on a CD40L/IL-4-activated murine B cell increases the rate of mature IgG1 transcription by increasing the level of NF-kappaB activation, as well as Oct-2 expression and binding to the 3'-IgH enhancer. The signal transduction pathway activated by CD86 proximal to NF-kappaB activation is unknown. In this study, we show that CD86 stimulation on an activated B cell increases the activity of PI3K and the phosphorylation of phosphoinositide-dependent kinase 1, Akt, and IkappaB kinase alphabeta. In addition, CD86 stimulation induces an increase in the phosphorylation of phospholipase Cgamma2 and protein kinase C alphabeta. CD86-mediated activation of these two signaling pathways leads to increased Oct-2 expression, increased gene activity mediated by NF-kappaB and 3'-IgH enhancer increased activity. These results identify a previously unknown signaling pathway induced by CD86 to regulate the level of B cell gene expression and activity.