CXCR4 and immunodeficiency disease: Here, we addressed this point using as a paradigm the WHIM Syndrome (WS), a rare immunodeficiency caused by viable inherited heterozygous gain-of-function mutations in CXCR4 affecting homologous desensitization of the receptor, thus resulting in enhanced signaling following CXCL12 stimulation, defective lymphoid differentiation of HSPCs and reduced blood leukocyte numbers47–50.