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

• Published in: Trends in immunology 2019-01, Vol.40 (1), p.35-48
• Main Authors: Moran, Imogen, Grootveld, Abigail K., Nguyen, Akira, Phan, Tri Giang
• Format: Article
• Language: English
• Subjects: Antigens; Cancer; Cell adhesion & migration; Computer memory; Effector cells; Immunological memory; Ligands; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Memory cells; Pathogens; Plasma cells; Sinuses
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2018.11.004

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. 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.