Figure 1.

The CXCL12/CXCR4 neutrophil retention axis. There is a substantial storage pool of mature neutrophils in the bone marrow termed the bone marrow reserve. Under homeostasis, neutrophils are retained in the bone marrow due to the constitutive production of CXCL12 by stromal cells and expression of CXCR4 by neutrophils. Genetic deletion of CXCR4 in myeloid cells (CXCR4MKO) results in depletion of the bone marrow reserve with a rise in circulating neutrophil numbers. In WHIM syndrome, a genetic mutation of CXCR4 increases the activity of the receptor, thereby enhancing neutrophil retention in the bone marrow and reducing numbers in the blood