International Immunology, Vol. 12, No. 8, 1167-1172,
August 2000
© 2000 Japanese Society for Immunology
NF-
B/p50 and NF-B/c-Rel differentially regulate the activity of the 3'
E-hsl,2 enhancer in normal murine B cells in an activation-dependent manner
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
Correspondence to: C. M. Snapper
The enhancer complex located 3' to the CH
gene in the IgH locus (3E) may regulate B cell function through its ability to act as a locus control region. Multiple, functionally relevant NF-
B binding sites are located within the 3'E. NF-B subunits, especially p50 and c-Rel, have also been shown to play critical and differential roles in regulating B cell proliferation, Ig secretion, germline CH transcription and Ig class switching. Thus, NF-B could regulate B cell function in part through modulation of 3'E activity. In this study we determined whether p50 and/or c-Rel regulate 3'E activity in normal murine B cells and whether this depends on the nature of the B cell activator. For this purpose, we crossed p50- and c-Rel-deficient mice with mice that are transgenic for a 3'E-hsl,2-human ß-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' E-hsl,2 activity in lipopolysaccharide-activated B cells, whereas c-Rel is required for optimal 3'E-hs1,2 induction in B cells activated through CD40.
Keywords: B lymphocytes, cellular activation, rodent, transcription factors, transgenic/knockout
Transmitting editor: K. Takatsu
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