Kin Nicholas W, Sanders Virginia M
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
J Immunol. 2006 Jun 1;176(11):6727-35. 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.
在CD40L/IL-4激活的小鼠B细胞上刺激CD86，通过增加NF-κB激活水平、Oct-2表达以及与3'-IgH增强子的结合，提高成熟IgG1转录速率。CD86在靠近NF-κB激活处激活的信号转导途径尚不清楚。在本研究中，我们发现激活的B细胞上的CD86刺激增加了PI3K的活性以及磷酸肌醇依赖性激酶1、Akt和IκB激酶αβ的磷酸化。此外，CD86刺激诱导磷脂酶Cγ2和蛋白激酶Cαβ的磷酸化增加。CD86介导的这两条信号通路的激活导致Oct-2表达增加、由NF-κB介导的基因活性增加以及3'-IgH增强子活性增加。这些结果确定了一条以前未知的由CD86诱导的信号通路，以调节B细胞基因表达和活性水平。
