Lymph node macrophages

Abstract

Lymph node (LN) macrophages have long been known for their efficient uptake of lymph-borne antigens. A convergence of studies on innate and adaptive immune responses has led to exciting recent advances in understanding their more specialized properties: presenting antigens to B cells, dendritic cells and T cells, producing trophic factors and cytokines, and, remarkably, being permissive for viral infection, a property critical for mounting anti-viral responses. LN macrophages have been traditionally divided into subsets based on their subcapsular sinus and medullary locations. Here, we classify LN macrophages into three subsets: subcapsular sinus macrophages, medullary sinus macrophages and medullary cord macrophages. We review the literature regarding the roles of these cells in innate and adaptive immune responses and requirements for their development. We also discuss challenges associated with their purification as well as the existence of additional heterogeneity among LN macrophages.

Fig. 1

Schematic of LN showing major zones and lymphatic sinuses and suggested nomenclature for macrophage subsets. Boxed regions are enlarged on the right to show more details. Upper box: SCS and interfollicular region with follicle shown in green shading, T zone in blue and interfollicular region in purple. Lower box: medullary region in cross-section showing medullary cords in light brown. Sinuses are shown in white and sinus-lining lymphatic endothelial cells are yellow. The macrophages are labeled based on the suggested SSM, MSM and MCM nomenclature discussed in the main text. Their CD169, CD11b and F4/80 phenotype is summarized, although it is not yet established whether the physical segregation of cells with the indicated MSM and MCM marker patterns is as distinct as shown. A DC is shown in dark blue (upper) and a polymorphonuclear cell in brown (lower). Reticular fibers within medullary sinuses are in grey. B = B cell; T = T cell; PC = plasma cell.

Fig. 2

CD169⁺ macrophage-derived blebs are acquired by lymphocytes. a LN cells prepared by enzymatic digestion [20] were stained for CD169 and CD11c and the frequency of CD169⁺CD11c^lo cells is shown. b LN cells stained for CD169, B220 and IL7Rα were FACS sorted for the intensity of CD169 staining shown in a, positive staining for IL7Rα, and lack of B220 staining. Image shows examples of sorted cells examined by immunofluorescence microscopy to detect CD169 (green) and IL7Rα (red).