NF-κB binds to the immunoglobulin Sγ3 region in vivo during class switch recombination
✍ Scribed by Lili Wang; Robert Wuerffel; Amy L. Kenter
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 288 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
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‐κB 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‐κB p50‐deficient mice. However, the pleiotropic contributions of NF‐κB to gene expression in B cells has made discerning a direct role for NF‐κB in CSR difficult. We now observe that binding of NF‐κB components p50 and p65 is detected on Sγ3 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‐κB recognition site in Sγ3 with the same temporal kinetics as found in the chromatin immunoprecipitation analysis. Binding of NF‐κB components p50 and p65 was also detected on Sγ1 following B cell activation. H3 histone hyper acetylation at Sγ1 is strongly correlated with NF‐κB binding, suggesting that NF‐κB mediates chromatin remodeling in the Sγ3 and Sγ1 region.