Multi-omics Analysis of naive B cells of patients harboring the C104R mutation in TACI

Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary immunodeficiency in humans. The genetic cause of CVID is still unknown in about 70% of cases. 10% of CVID patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (TNFRSF13B), encoding TACI. Mutations in TNFRSF13B alone may not be sufficient for the development of CVID, as 1% of the healthy population carry these mutations. The common hypothesis is that TACI mutations are not fully penetrant and additional factors contribute to the development of CVID. To determine these additional factors, we investigated the perturbations of transcription factor binding and the transcriptome profiles in unstimulated and CD40L/IL21-stimulated naive B cells from CVID patients harboring the C104R mutation in TNFRSF13B, and compared them to their healthy relatives with the same mutation. In addition, the proteome of stimulated naive B cells was investigated. For functional validation, intracellular protein concentrations were measured by flow cytometry.