A G protein-associated ERK pathway is involved in LPS-induced proliferation and a PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in resting B cells.

We, previously, showed that PKC-dependent ERK/p38 MAPK activation was inhibited by treating the resting B cell line 38B9 with an anti-MHC class II antibody. Further studies in this work demonstrated that PKA was involved in lipopolysaccharide (LPS)-induced proliferation of the cells, such that the PKC inhibitor activated PKA with concomitant LPS-induced proliferation but not IgG secretion. Consequently, the PKA inhibitor down-regulated ERK and p38 MAPK, and decreased cell proliferation. In addition, the treatment of LPS-stimulated 38B9 cells with PTK inhibitor reduced PKC- and PKA-dependent p38 MAPK activation and reduced the level of IgG secretion rather than the level of proliferation. However, the treatment of LPS-stimulated 38B9 cells with pertussis toxin (PTX), an inhibitor for the G protein-coupled receptor, inhibited the activation of both PKC- and PKA-dependent ERK and significantly reduced LPS-induced proliferation but not IgG secretion. Furthermore, ERK and p38 MAPK inhibitors reduced LPS-induced proliferation and differentiation, respectively, in 38B9 cells in a dose-dependent manner. These results suggest that LPS-induced proliferation of resting B cells is mainly mediated through a G protein-associated PKA/PKC-dependent ERK pathway and that a PTK-associated PKC/PKA-dependent p38 MAPK pathway is mostly involved in LPS-induced differentiation of the resting B cells.