Figure 1.

Neutrophil Populations in Homeostatic Conditions.

Humans: neutrophils mature in the bone marrow (BM) from committed myeloid precursors that, through subsequent differentiation stages (here defined as ‘immature neutrophils’), differentiate into segmented mature neutrophils [31]. Under resting conditions, only terminally differentiated neutrophils are released into the circulation and recovered as normal-density neutrophils (NDNs) (Box 1) [54]. Current evidence suggests that different neutrophil subpopulations, defined by the indicated markers, are present in human blood under homeostatic conditions 5., 6., 8., 21., 30., 36., 37.. Under resting conditions, neutrophils are also marginated in pools within the lungs, spleen, and liver, but the phenotypes and functions of these cells remain poorly defined 5., 6., 9.. A unique population of human neutrophils was found in the marginal zone (MZ) of the spleen, and these were termed B cell helper neutrophils (N_BH cells) owing to their robust B cell-activating properties [39]. Mice: mouse neutrophil development within the BM comprises three distinct subpopulations, namely preNeu (proliferative neutrophil precursor), immature, and mature neutrophils [33]. As observed in humans, based on differential surface marker expression, circulating mouse neutrophils exhibit heterogeneity that associates with distinct effector activities 5., 37., 40., 41., 42., 43.. In mice as in humans, neutrophils not only marginate in the spleen, liver, and lung vasculature but also transit and reside in other organs such as muscle, skin, lymph nodes, and intestine [44]. In the mouse spleen, three neutrophil subpopulations localized in the red pulp or MZ participate in emergency granulopoiesis (Ly6G^int) and pneumococcal clearance (Ly6G^high) [48], and can regulate antibody production in MZ B cells (NB_H, as observed in humans) [47].