NF-kappa B binds to the immunoglobulin S gamma 3 region in vivo during class switch recombination.
Ig class switch recombination (CSR) is dependent upon the expression of activation-induced deaminase and targeted to specific isotypes by germ-line transcript expression and isotype-specific factors. NF-kappaB plays critical roles in multiple aspects of B cell biology and has been implicated in the mechanism of CSR by in vitro binding assays and altered S/S junctions derived from NF-kappaB p50-deficient mice. However, the pleiotropic contributions of NF-kappaB to gene expression in B cells has made discerning a direct role for NF-kappaB in CSR difficult. We now observe that binding of NF-kappaB components p50 and p65 is detected on Sgamma3 in vivo following lipopolysaccharide (LPS) activation and repressed by LPS + IL-4, suggesting a direct role for this factor in CSR. In vivo footprinting confirms occupancy of a previously defined NF-kappaB recognition site in Sgamma3 with the same temporal kinetics as found in the chromatin immunoprecipitation analysis. Binding of NF-kappaB components p50 and p65 was also detected on Sgamma1 following B cell activation. H3 histone hyper acetylation at Sgamma1 is strongly correlated with NF-kappaB binding, suggesting that NF-kappaB mediates chromatin remodeling in the Sgamma3 and Sgamma1 region.
Wang
Lili
L
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA.
Wuerffel
Robert
R
Kenter
Amy L
AL
D000818:Animals; D001666:Binding Sites, Antibody / Q000235:genetics; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic
D007142:Immunoglobulin gamma-Chains; D016328:NF-kappa B