These results support the dysregulation of NF-κB and ERK signaling in naïve B cells of C104R TACI mutation carriers and may possibly point towards novel targets not only for the treatment of TACI mutation carriers but also for patients with CVID of unknown genetic cause and patients with lymphoproliferation and autoimmunity in general, which is the predominant phenotype seen in our C104R-TACI-mutated individuals. This evidence concerns the gene TNFRSF13B and common variable immunodeficiency.