Tumour necrosis factor receptor‐1 is dispensable for the migration of marginal metallophilic macrophages into the B‐cell zone of the mouse spleen

Abstract

The spleen is the only blood filter in the organism which removes foreign antigens and effete cells from circulation. The significant role in capturing, transporting and presentation of antigens to immune cells is executed by a special subset of splenic macrophages called marginal metallophilic macrophages. Upon stimulation with lipopolysaccharide, these cells promptly migrate from their preferential location at the inner aspect of the splenic marginal sinus into the B-cell lymphoid follicles. This migration is executed via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion. However, the role of tumour necrosis factor-α/tumour necrosis factor receptor-1 signalling axis has not been studied, despite its critical role in the formation of B-cell lymphoid follicles, follicular dendritic cell networks and germinal centres. Here, we show that signalling via tumour necrosis factor receptor-1 is not required for the migration of marginal metallophilic macrophages into the B-cell zone and that the presence of organized B-cell lymphoid follicles is not a prerequisite for their dislocation.

Macrophage‐fibroblast circuits in the spleen

“…39,[91][92][93] Interestingly, upon stimulation with LPS or chimeric Fc protein targeting CD169, MMM migrate from the marginal sinus into B follicles, providing further evidence that they also contribute to the regulation of B cell immunity. [94][95][96][97] While this remains to be formally demonstrated, MMM might even recruit follicular B cells. Activated splenic follicular B cells express Epstein-Barr virusinduced G protein-coupled receptor 2, and migrate toward the MZ in response to its endogenous ligand oxysterol (such as 7a,25dihydroxycholesterol).…”

“…• regulation of germinal center B cells' development 73 • regulation of germinal center reaction 73 MMM MZ CD169 + , MHCII + , MOMA-1 + • clearance of blood-borne apoptotic cells, pathogens (Listeria monocytogenes, Leishmania donovani, lymphocytic choriomeningitis virus, adenovirus, murine cytomegalovirus, cowpox virus) 1,3,76-79,81,82 • transfer of antigens to cross-presenting splenic DC 90 • a directly involved in the activation of follicular B cells through antigen presentation and secretion of chemotactic cues [94][95][96][97]99,100 TZM WP, T zone MerTK + , CX3CR1 + • phagocytosis of apoptotic T cells 107 TBM WP, Germinal Center CD68 + , MFG-E + 8, MerTK + , Tim4 + , CD36 + • phagocytosis of apoptotic B cells [104][105][106] a Potential functions of splenic macrophages.…”

“…Imaging studies have shown that they capture opsonized antigens and viral parti-cles from lymph and present them to B cells for subsequent follicular delivery 39,[91][92][93]. Interestingly, upon stimulation with LPS or chimeric Fc protein targeting CD169, MMM migrate from the marginal sinus into B follicles, providing further evidence that they also contribute to the regulation of B cell immunity [94][95][96][97]. While this remains to be formally demonstrated, MMM might even recruit follicular B cells.…”