Bone marrow SDF-1 immunohistochemistry and model of late-onset neutropenia. (A) SDF-1 detection in the bone marrow of a patient with LON. SDF-1 is expressed by bone marrow stromal cells, which are dispersed throughout the bone marrow; osteoblasts that are juxtaposed to the bone trabeculae; and endothelial cells that line the blood capillaries. Sections immunostained for SDF-1 with specific antibodies. Images were collected using a Nikon Eclipse 6600 microscope (10×/0.45 DICL and 40×/0.95 DICM lenses; Nikon, Tokyo, Japan) with a Retiga 1300 digital camera (QImaging, Burnaby, BC, Canada) and IP Lab acquisition software (Scanalytics, Fairfax, VA). Images were imported into Adobe Photoshop software (Adobe Systems, San Jose, CA). (B) A model of late-onset neutropenia is shown. Early B-cell lymphopoiesis and neutrophil egress into the bone marrow sinusoid is regulated by SDF-1 gradients (dark to light shading, left) within the bone marrow microenvironment, as shown on the left. In a patient with LON, we hypothesize that the SDF-1 gradients are transiently disrupted (even gray shading, right) within the bone marrow microenvironment due to SDF-1 consumption by rapidly expanding B cells, resulting in the temporary inhibition of neutrophil egress across the sinusoid, as shown on the right. SDF-1–positive cells are indicated by arrows.