The dysregulation of relevant genes for B-cell activation such as CD79A, CD79B, CD22, CD72, and PTPN6, all of them genes involved in the modulation of the B-cell receptor pathway, specifically upon anti-CD3/CD28 treatment (indirect B-cell activation via T-cell stimulation) and not upon CD40L + IL-21 treatment (direct B-cell stimulation), would suggest the existence of extrinsic B-cell defects that might contribute to the impaired B-cell responses observed in CVID patients. This evidence concerns the gene CD28 and common variable immunodeficiency.