NF-kappa B/p50 and NF-kappa B/c-Rel differentially regulate the activity of the 3 'alpha E-hsl,2 enhancer in normal murine B cells in an activation-dependent manner
P. Zelazowski et al., NF-kappa B/p50 and NF-kappa B/c-Rel differentially regulate the activity of the 3 'alpha E-hsl,2 enhancer in normal murine B cells in an activation-dependent manner, INT IMMUNOL, 12(8), 2000, pp. 1167-1172
The enhancer complex located 3' to the C(H)alpha gene in the IgH locus (3 a
lpha E) may regulate a cell function through its ability to act as a locus
control region. Multiple, functionally relevant NF-kappa B binding sites ar
e located within the 3'alpha E, NF-kappa B subunits, especially p50 and c-R
el, have also been shown to play critical and differential roles in regulat
ing a cell proliferation, Ig secretion, germline CH transcription and Ig cl
ass switching. Thus, NF-kappa B could regulate a cell function in part thro
ugh modulation of 3'alpha E activity. In this study we determined whether p
50 and/or c-Rel regulate 3'alpha E activity in normal murine a cells and wh
ether this depends on the nature of the a cell activator. For this purpose,
we crossed p50- and c-Rel-deficient mice with mice that are transgenic for
a 3'alpha E-hsl,2-human beta-globin reporter gene, and established p50(-/-
) or c-Rel(-/-) mice homozygous for the enhancer transgene. We show, using
optimal stimulating conditions, that p50 selectively augments 3'alpha E-hs1
,2 activity in lipopolysaccharide-activated a cells, whereas c-Rel is requi
red for optimal 3'alpha E-hs1,2 induction in a cells activated through CD40
.