A. Dinkel et al., TRANSCRIPTION FACTOR EGR-1 ACTIVITY DOWN-REGULATES FAS AND CD23 EXPRESSION IN B-CELLS, The Journal of immunology, 159(6), 1997, pp. 2678-2684
Activation of mature B cells via Ag receptor cross-linking induces tra
nsient expression of the transcription factor Egr-1. Although the acti
vating signals leading to Egr-1 induction have been studied extensivel
y, little is known about the genes that are placed further downstream
within this activation cascade and that are transcriptionally regulate
d by Egr-1. To identify such target genes, we established Egr-1-overex
pressing transfectants from the murine B cell line K46 and from human
Ramos B cells. All clones derived from K46 B cells showed increased ex
pression of CD44. Most interestingly, expression of CD95 (Fas/Apo-1) a
nd of CD23 was down-regulated in all K46 transfectants. As a consequen
ce, they became resistant to apoptosis induced by anti-CD95 Ab treatme
nt. Similarly, the Egr-1-expressing Ramos cells showed reduced levels
of CD95 expression. Thus, Egr-1 seems to control the expression of dow
nstream target genes not only as a transcriptional activator, but also
as a repressor molecule. In B cells, Egr-1 therefore plays a critical
role in integrating the short-lived signal delivered by triggering of
the Ag receptor into phenotypic changes, including repression of CD95
and CD23 transcription.