CXCR3-mediated signal transduction events in T-blasts in response to IP-10 and ITAC stimulation

Abstract

The NF-KB/Rel transcription factors play an important role in the expression of genes involved in B cell development, differentiation and function. Although it is clear that BCR stimulation leads to the activation of NF-KB and despite the importance of NF-KB to B cell function, little is known about the signaling pathways leading to NF-KB activation. We will address the role of PI 3-kinase in BCRand LPS-induced NF-KB activation in primary murine B cells. Using PI 3-kinase inhibitors, we demonstrate that PI 3-kianse activity is vital for BCR-induced NF-KB DNA-binding activity.Furthermore, we show that this is achieved via PKCdependent degradation of I K B~. Similarly, we show that PI 3-kinase is also required for LPS-induced NF-KB-DNA binding activity and I K B~ degradation. Interestingly, blocking PKC activity did not affect the degradation of I K B~ after LPS stimulation. This suggests the involvement of PI 3-kinase in at least two distinct signaling pathways leading to activation of NF-KB in B cells.90 Ma1 (MyD88 adapter-like) is a novel Toll IL-1 receptor (TIR)