CD86 stimulation on a B cell activates the phosphatidylinositol 3-kinase/Akt and phospholipase C gamma 2/protein kinase C alpha beta signaling pathways.
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.
Kin
Nicholas W
NW
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
Sanders
Virginia M
VM
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005260:Female; D051550:I-kappa B Kinase / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050813:Octamer Transcription Factor-2 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
D051940:B7-2 Antigen; D007143:Immunoglobulin Heavy Chains; D007527:Isoenzymes; D016328:NF-kappa B; D050813:Octamer Transcription Factor-2; C489206:Pou2f2 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051966:Phospholipase C gamma