However, all four molecular genetic defects underlying CVID reported to date, namely ICOS [13], TACI [15,16], CD19 [17] and BAFF-R [31] were identified by a candidate gene approach using either phenotypic or genetic screening of genes known to be involved in B cell homeostasis, B cell activation or the T- B cell interaction. This evidence concerns the gene ICOS and common variable immunodeficiency.