New Insights into the Cell Biology of the Marginal Zone of the Spleen

Abstract

In the marginal zone of the spleen the bloodstream passes through an open system of reticular cells and fibers in which various myeloid and lymphoid cells are located. Macrophages in this region are well equipped to recognize pathogens and filter the blood by virtue of unique combinations of pattern recognition receptors. They interact with a specific set of B cells that can be found only in the marginal zone and that are able to react rapidly to bacterial antigens in particular. This combination of strategically located cells is an important factor in our defense against blood-borne pathogens. New data on the development of the marginal zone itself and the marginal zone B cells are reviewed and discussed in light of the function of the spleen in host defense.

SIGNR1-Negative Red Pulp Macrophages Protect against Acute Streptococcal Sepsis after Leishmania donovani-Induced Loss of Marginal Zone Macrophages

“…Once S. pneumoniae access the bloodstream, host protection is thought to be dependent on the efficient SIGNR1-mediated binding of bacteria by MZMs as blood is filtered by the splenic marginal zone. 1,3,9,10 On this basis, we had hypothesized that disruption of the marginal zone or reduction in numbers of MZMs might severely affect the ability to handle blood-borne S. pneumoniae infection. Surprisingly, however, L. donovani-infected mice exhibited enhanced protection against subsequent S. pneumoniae challenge.…”

“…1 In the murine spleen, blood enters the marginal zone, a distinct anatomical microenvironment dominated by two macrophage populations: the marginal zone macrophages (MZMs) that face the red pulp and the marginal metallophilic macrophages (MMMs) that face inwards to the white pulp (reviewed in Ref. 1 ).…”

“…1 In the murine spleen, blood enters the marginal zone, a distinct anatomical microenvironment dominated by two macrophage populations: the marginal zone macrophages (MZMs) that face the red pulp and the marginal metallophilic macrophages (MMMs) that face inwards to the white pulp (reviewed in Ref. 1 ). The marginal zone is therefore an important site for rapid capture of blood-borne bacterial, 2,3 viral, 4 and protozoal 5 pathogens and although MZMs are most often attributed with the greatest phagocytic activity, MMMs also display this property.…”

The macrophage: Past, present and future

“…Some tissue populations of macrophage-related cells, e.g. in the marginal zone of the spleen [51], have a distinctive phenotype, but with a poorly defined origin. Even more distinct are plasmacytoid DC, which express both myeloid and lymphoid markers, as well as the potent ability to produce type I IFN [52].…”

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

“…As an organ with immune function, spleen contains multiple cell populations capable of responding to both innate and acquired arms of immunity. Innate immune cells positioned in the marginal zone (MZ) of spleen react quickly to bloodborne bacteria and viruses, clearing pathogens via macrophagemediated phagocytosis and Ab release into the bloodstream following B cell activation (1). Without a rapid innate immune response, asplenic patients face a risk of overwhelming postsplenectomy infection, especially from encapsulated bacteria such as Streptococcus pneumoniae (2).…”