Rac/ROS-related protein kinase C and phosphatidylinositol-3-kinase signaling are involved in a negative regulating cascade in B cell activation by antibody-mediated cross-linking of MHC class II molecules

In addition to their essential role in antigen presentation, MHC class II molecules have been widely described as receptors associated with signal transduction involved in regulating B cell function. However, their precise function and mechanism in signal transduction are not yet fully elucidated. Our previous studies demonstrated that cross-linking of MHC class II molecules led to the inhibition of resting B cell activation in which various signal molecules were involved. Especially, Rac-associated ROS-dependent MAP kinases, including ERK1/2 and p38, are involved in MHC class II-associated negative signal transduction in the phorbol 12, 13-dibutyrate (PDBU)-treated, but not LPS-treated, resting B cell line, 38B9. In this study, we further illustrated that PKC regulates downstream signal molecules, including MAP kinases and NF-κB in PDBU-stimulated resting B cells, together with Rac and ROS. In addition, we found that phosphatidylinositol 3-kinase (PI3K)-dependent activation of ERK/p38 MAP kinases was associated with the signaling procedure in PDBU-induced B cell activation. Collectively, Rac/ROS-related PKC and PI3K signaling are involved in a negative regulation cascade through the cross-linking of MHC class II molecules by anti-MHC class II antibodies in resting B cells.