Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID)
J. Clin. Invest. Lilit Garibyan, et al. 117:1550 doi:10.1172/JCI31023 [
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Figure 10C104R hTACI dominantly interferes with signaling, but not ligand binding, by WT hTACI. hTACI surface expression (
A) and rhBAFF binding (
B) by 293T cells transfected with 1 μg of WT hTACI, 1 μg of C104R hTACI alone, or 1 μg of each together. (
C) 293T cells were transfected with 10 ng WT mTACI alone, 10 ng C104R mTACI alone, or 10 ng of each together along with 0.5 mg of NF-κB–luc reporter plasmid and 10 ng control pRL-null plasmid. Equal amounts of DNA were used for each transfection by using empty vector DNA when needed. After 4 hours, recombinant hBAFF (0.1 μg/ml) was added, and reporter gene activity was determined 20 hours later. NF-κB luciferase induction was normalized to
Renilla luciferase intensity. Values represent the fold increase by BAFF stimulation compared with unstimulated sample and are the mean ± SEM from 6 independent experiments.