TACI Deficiency Enhances Antibody Avidity and Clearance of an Intestinal Pathogen

Tsuji S, et al., 124(11):4857-66, J Clin Invest, 2014

The authors performed an investigation to understand the phenotype of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) deficiency in mice. The mice lacking TACI exhibit hypogammaglobulinemia and generate defective long-lived antibody responses. These features are consistent with the human phenotype of common variable immunodeficiency (CVID). Those individuals with CVID express either the C104R or A181E mutants of TACI. Since TACI deficient mice can produce bursts of IgG, the authors tested whether those antibodies produced by TACI deficient mice attain the same avidity and functions of those produced by normal mice. The study revealed such antibodies produced in bursts attain higher avidity and the mice were able to rapidly clear Citrobacter rodentium, a pathogen known for severe human enteritis. An Octet RED system was used in the determination of KD for 4-hydroxy-3-nitrophenylacetyl (NP) antigen specific IgGs. A biotinylated version of NP4-BSA captured onto SSA biosensors used in the analyses.

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