This model of BLyS/B-cell interaction is strongly supported in X-linked agammaglobulinemia patients and in several animal models where mature Blys-receptor+ B-cells were not generated, and where soluble BLys levels were then found higher than that in healthy controls while in other genetically defined primary immunodeficiencies, patients who show switched BlyS receptor positive memory B-cells, have normal BlyS levels [61]. The gene discussed is TNFSF13B; the disease is isolated agammaglobulinemia.