Ar. Gottschalk et al., FC-GAMMA-RII CROSS-LINKING INHIBITS ANTI-IG-INDUCED EGR-1 AND EGR-2 EXPRESSION IN BCL(1), The Journal of immunology, 152(5), 1994, pp. 2115-2122
Activation of B cells through their Ag receptor is known to be negativ
ely regulated by Fc gamma RII engagement. To explore the molecular and
biochemical mechanisms of Fc gamma RII-mediated inhibition, we invest
igated the effect of Fc gamma RII engagement on the expression of two
immediate-early genes, egr-1 and egr-2, and tyrosine phosphorylation e
vents following the activation of the murine B cell line, BCL(1). Egr-
1 and egr-2 were expressed in BCL(1) after slg cross-linking. The indu
ction of egr-1 and egr-2 expression was prevented when the Fc gamma RI
I was co-cross-linked with sIg in BCL(1), but not in WEHI-231. The inh
ibitory effects of Fc gamma RII engagement on egr-1 and egr-2 expressi
on occurred when the Fc gamma RII was cross-linked with either sIgM or
sIgD. Treatment with cyclosporin A prevented the expression of egr-2
induced by sig cross-linking, but did not inhibit egr-1 expression. In
addition, cyclosporin A did not prevent the negative-regulatory effec
ts of Fc gamma RII engagement on egr-1 expression, suggesting that the
Fc gamma RII works upstream from the site of action of cyclosporin A,
To investigate activation signals more proximal to the plasma membran
e, we compared tyrosine phosphorylation patterns of several effector m
olecules known to play a role in B cell activation. Cross-linking of s
Ig induced tyrosine phosphorylation of the p62 CAP-associated protein.
The p62 protein became hyperphosphorylated in response to co-cross-li
nking of sIg with Fc gamma RII. Our results identify egr-1 and egr-2 a
s targets of Fc gamma RII-mediated inhibition of anti-Ig-induced B cel
l activation. In addition, they show that negative regulation by Fc ga
mma RII is effective in both cyclosporin A-sensitive and insensitive p
athways. Further, we suggest a possible Fc gamma RII signaling pathway
leading to the inhibition of egr-1 and egr-2 expression.