Subcapsular Sinus Macrophages: The Seat of Innate and Adaptive Memory in Murine Lymph Nodes

SCS macrophages, lymphatic endothelial cells, and marginal reticular cells create the subcapsular niche in the lymph node that acts as a barrier to pathogen entry. Innate effector cells and adaptive memory cells are pre-positioned in the subcapsular niche. SCS macrophages present antigen to naïve B cells, CD8+ T cells, and invariant natural killer T cells in the primary response, and to Bmems and possibly to memory CD8+ T cells and follicular memory T cells in the secondary response. SCS macrophages prevent systemic dissemination of lymph-borne pathogen by initiating an inflammatory immune response in the subcapsular region to activate and recruit innate and adaptive immune cells. SCS macrophages can reactivate Bmems to differentiate into plasma cells in the SPF, a site of rapid, high-output plasma cell differentiation. Subcapsular sinus (SCS) macrophages are strategically positioned at the lymph–tissue interface in the lymph node to trap and present antigen to B cells. Recent murine data has shown that SCS macrophages also prevent the systemic spread of lymph-borne pathogens and are capable of activating a diverse range of innate effector and adaptive memory cells, including follicular memory T cells and memory B cells (Bmems), that are either pre-positioned or rapidly recruited to the subcapsular niche following infection and inflammation. Furthermore, Bmems are rapidly reactivated to differentiate into plasma cells in subcapsular proliferative foci (SPF). Thus, understanding how SCS macrophages coordinate both innate and adaptive memory responses in the subcapsular niche can provide new opportunities to bolster immunity against pathogens and cancer. Subcapsular sinus (SCS) macrophages are strategically positioned at the lymph–tissue interface in the lymph node to trap and present antigen to B cells. Recent murine data has shown that SCS macrophages also prevent the systemic spread of lymph-borne pathogens and are capable of activating a diverse range of innate effector and adaptive memory cells, including follicular memory T cells and memory B cells (Bmems), that are either pre-positioned or rapidly recruited to the subcapsular niche following infection and inflammation. Furthermore, Bmems are rapidly reactivated to differentiate into plasma cells in subcapsular proliferative foci (SPF). Thus, understanding how SCS macrophages coordinate both innate and adaptive memory responses in the subcapsular niche can provide new opportunities to bolster immunity against pathogens and cancer. a region in the lymph node cortex populated by B cells. The follicles are separated by the interfollicular region (IFR) lacking B cells that is populated by both F4/80+ SCS macrophages and F4/80neg MSMs, as well as by CCL19lo TRCs. The IFR also contains cortical lymphatic sinuses and high endothelial venules (HEVs) that are involved in lymphocyte trafficking into and out of the lymph node. also known as sialoadhesin, sialic acid-binding IgG-like lectin-1 (Siglec1), CD169 is an immunoglobulin superfamily I-type lectin that is constitutively expressed by lymph node-resident SCS macrophages and MSMs, splenic marginal metallophilic macrophages, bone marrow macrophages, and macrophages in the intestinal lamina propria. It can also be induced on monocytes, macrophages, and dendritic cells (DCs) by type I IFN. the process of tracking the origin and fate of cells during development and in response to physiological and pathological stresses. This can be facilitated by photoconversion, optically marking cells of interest by switching the fluorescence emission of the cell from one color (e.g., green) to another (e.g., red). CD4+ memory T cells residing in the B cell follicle. multiprotein complex of innate immune receptors and sensors that induce inflammation in response to infection and cellular stress by activation of caspase 1 and induction of IL-1β and IL-18. It also induces an inflammatory form of cell death called pyroptosis. these are derived from common lymphoid progenitors that lack expression of B cell and T cell receptors for antigen. They are distinct from unconventional T cells such as γδ T cells which express rearranged γδ T cell receptors, and natural killer T (NKT) cells which express rearranged αβ T cell receptors. stromal cell positioned beneath the floor of the SCS. a specialized subset of CD169+CD11b+CD11cintF4/80+ macrophages predominantly lining the medullary sinus, and some line the SCS and cortical lymphatic sinuses in the interfollicular region (IFR). long-lived B cells previously activated by antigen that are able to generate faster and stronger responses upon antigen recall. a subset that specializes in the production of type I IFN in antiviral defense and in autoimmune diseases such as systemic lupus erythematosus. a spongiform encephalopathy that is transmissible in humans and animals by ingestion or by exposure to infected tissue; it causes a progressive fatal neurodegenerative disorder. specialized microenvironment in the subcapsular region in the outer B cell follicle created by SCS macrophages, lymphatic endothelial cells (LECs), and MRCs. It provides a barrier function to prevent pathogen entry as well as the machinery that is necessary to recruit and activate innate effector and adaptive memory cells to generate adaptive immunity. an endothelium-lined space directly below the capsule where afferent lymph drains into the lymph node. a specialized subset (CD169+CD11b+CD11cintF4/80neg) of macrophages that line the SCS, predominantly overlaying the B cell follicle. They have a similar phenotype and ontogeny to marginal metallophilic macrophages lining the blood-filled marginal sinus in the spleen. an extensive structure in the subcapsular region covering the cortical surface of the B cell follicle where Bmems are reactivated to proliferate and differentiate into plasma cells. CCL19+ stromal cells in the T cell zone in the lymph node parenchyma. Previously termed fibroblastic reticular cells (FRCs).