N. Sakata et al., Differential activation and regulation of mitogen-activated protein kinases through the antigen receptor and CD40 in human B cells, EUR J IMMUN, 29(9), 1999, pp. 2999-3008
In human B cells, antigen receptor ligation and CD40 ligation are known to
activate the extracellular-regulated kinases (ERK) and c-Jun N-terminal kin
ase (JNK) pathways, which in turn regulate many important B cell functions.
We previously reported that antigen receptor ligation activated the ERK pa
thway whereas CD40 ligation activated the JNK/stress-activated protein kina
se (SAPK) pathway. Here, we demonstrate that another SAPK, p38/Hog1, is act
ivated by both antigen receptor ligation or CD40 ligation in a human B-lymp
hoblastoid cell line and tonsillar B cells. Wortmannin, an inhibitor of pho
sphatidylinositol 3-kinase, partially inhibited ERK2 and p38 activation tri
ggered through the B cell receptor whereas activation of JNK1 and p38 throu
gh CD40 was not affected. PD98059, a specific inhibitor of mitogen-activate
d extracellular response kinase kinase (MEK), significantly inhibited ERK2
activation and partially inhibited p38 activation triggered by anti-lgM ant
ibody treatment, but did not affect CD40-dependent signaling events. In add
ition, anti-lgM antibody-induced signaling pathways were shown to be PKC-de
pendent in contrast to the CD40-induced signaling pathways. Thus, the B cel
l receptor and CD40 recruit the ERK, JNK and p38 pathways by using differen
t upstream effecters.