Localization and function of mature lymphocytes in the BM. Sinusoidal endothelial cells and perivascular C-X-C motif chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells are important constituents of HSC niches and form a topologically complex network to which many other BM cells connect. (A) Plasmablasts (PB) colocalize with perisinusoidal CAR cells. Here, they receive important survival signals such as B lymphocyte stimulator (BLyS), interleukin-6 (IL-6), and a proliferation-inducing ligand (APRIL), which enable them to differentiate into long-lived immunoglobulin-secreting plasma cells (PCs). Plasma cells are closely associated with BM regulatory T cells (T_REGS), dendritic cells (DCs), and eosinophils (Eos). During various clinical conditions, the BM can contain germinal centers, complete with follicular DCs (FDCs) and T follicular helper (T_FH) cells. The BM contains significant numbers of memory B cells (B_MEM), the majority of which are noncirculating BM resident cells that dock onto VCAM-1⁺ stromal cells. (B) Scattered naïve CD8⁺ T cells (CD8⁺ T_naïve) cluster at a 10:1 ratio around antigen-presenting cells (APCs) presenting their cognate antigen. Both naïve and memory CD8⁺ T cells (CD8⁺ T_MEM) locate close to the sinusoidal vessel and perivascular VCAM-1⁺ stromal cells that support their survival and maintenance by producing IL-7 and IL-15. Memory CD8⁺ T cells produce tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which can regulate or disrupt HSC maintenance, depending on the amount produced. Memory CD4⁺ T cells (CD4⁺ T_MEM) colocalize with VCAM-1⁺ stromal cells, which also produce IL-7. They secrete cytokines necessary for HSC maintenance, such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Tregs preserve normal hematopoiesis because of their T-cell suppressive function and possibly because of their IL-10 secretion. CD150^hi Tregs and CD4⁺ T cells localize near HSCs in the perivascular niche and provide immune privilege. Extracellular adenosine generated via CD39 expressed on those lymphocyte subsets maintains HSC quiescence. (C-D) The BM also contains mature γδ T cells, natural killer (NK) cells, NK T cells (NKT cells), and innate lymphoid cells (ILCs), but little is known about their precise localizations and functions. (C) BM NKT cells can be activated by CD1d-expressing HSCs and enhance myelopoiesis by secreting GM-CSF. BM NKT cells also secrete IFN-γ, IL-10, and IL-4, suggesting that they regulate hematopoiesis. Whether γδ T cells regulate hematopoiesis, as has been shown for αβ T cells, is not known. (D) The presence of ILC2s and ILC3s in the BM has been reported for mice and humans, respectively. ILC3s in human BM may be harbored in a stromal cell niche, but systematic analyses of the presence, localization, and function of mature ILCs in the BM are still lacking. In humans and mice, BM NK cells are a major source of cytokines that can regulate hematopoiesis, including IFN-γ, TNF-α, and GM-CSF. In a mouse Toxoplasma gondii infection model, BM NK cells triggered by systemic IL-12 produced IFN-γ, promoting an immune regulatory program in monocytes (Mono).