The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. (Some sources consider it to be the part of red pulp which borders on the white pulp, while other sources consider it to be neither red pulp nor white pulp.)
It is composed of cells derived primarily from the myeloid compartment of bone marrow differentiation. More recently, a population of neutrophil-killers has been described to populate peripheral areas of the marginal zone. At least three distinct cellular markers can be used to identify cells of the marginal zone, MOMA-1, ERTR-9 and MARCO.
The marginal zone (MZ) is a highly transited area that receives large amounts of blood from the general circulation. Remarkably, the splenic microvasculature shows striking differences in mice and humans. In humans, the spleen receives blood from the splenic artery, which branches into central and penicillar arterioles. Owing to the absence of a histologically defined marginal sinus, the blood flowing in penicillar arterioles directly drains into capillaries of the red pulp and perifollicular zone. The perifollicular zone is a well-defined area of decreased resistance that separates the MZ from the red pulp. Both the perifollicular zone and the red pulp consist of an open circulatory system of blood-filled spaces known as splenic cords, which have no defined endothelial delimitation and are in close contact with the venous sinusoidal vessels of the red pulp.
Experiments have shown that inert latex beads as well as live bacteria such as Escherichia coli and Listeria monocytogenes are trapped by the marginal zone. However, only immunogenic substances, i.e. bacteria, are trafficked to the T and B cell zones of the white-pulp and are efficiently presented to elicit an immune response.
Marginal zone lymphocytes are a type of B cell (Marginal-zone B cell, abbreviated "MZ B cell") created there, capable of binding IgM-antigen complexes. They are notable for their ability to serve several different roles in the immune system. MZ B cells express polyreactive BCRs that bind to multiple microbial molecular patterns.
Marginal Zone MacrophagesEdit
Within the marginal zone there exists two types of macrophages that are unique to this area: the marginal zone macrophages and the marginal metallophilic macrophages. These two macrophage sub-types are characterized by the expression of SIGN-R1 on the marginal zone macrophages and CD169 (siglec-1, sialoadhesin) on the marginal metallophilic macrophages.
In addition to the marginal zone B-cells that normally reside there, a number of other cell types that are present in the blood pass through the marginal zone e.g. lymphocytes and granulocytes. In addition, a large number of dendritic cells are thought to reside temporarily in the marginal zone before migrating into the white pulp following stimulation and antigen uptake, as well as a large number of lymphocytes remaining in the marginal zone for a period of time during the process of transmigration into the white pulp. It can be assumed that both these cells wills interact with the marginal zone macrophages.
Recent studies have shown that the marginal zone macrophages possess both important innate functions, as well as being able to promote adaptive immune responses, so these macrophages can bridge the innate and adaptive immunity.
The marginal zone macrophages have a variety of functions, one of which is the phagocytosis of blood-borne pathogens. Because of the anatomy of the marginal zone, the blood within it slows down and therefore the pathogens present in the systemic circulation are phagocytosed by both marginal zone macrophages. There is limited data regarding the specific roles of these two macrophage subsets in the uptake and eradication of pathogens. However there is evidence and reports that show there is a specific involvement of the various pathogen receptors on the marginal zone macrophages in recognising and eliminating certain pathogens, especially encapsulated bacteria. For example, the C-type lectin SIGN-R1 receptor (present on the marginal zone macrophages), mediates the recognition of pneumococcal saccharides and is necessary for Streptococcus pneumoniae clearance.
Furthermore, both types of marginal zone macrophages in the clearance and degradation of viruses e.g. cowpox virus and adenovirus serotype 5. Evidence has shown that the clearance of lymphocytic choriomeningitis virus by marginal zone macrophages is crucial to prevent the spreading of viral infections to peripheral organs.
- "Lymph nodes & spleen, nonlymphoma".
- Puga, Irene; Cols, Montserrat; Barra, Carolina M; He, Bing; Cassis, Linda; Gentile, Maurizio; Chen, Kang; Cerutti, Andrea (December 2011). "B cell–helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen". Nature Immunology. 13 (2): 170–80. doi:10.1038/ni.2194. PMC 3262910. PMID 22197976.
- Mebius, Reina E.; Kraal, Georg (August 2005). "Structure and function of the spleen". Nature Reviews Immunology. 5 (1): 606–616. doi:10.1038/nri1669. PMID 16056254. S2CID 3258595.
- Steiniger, Birte; Timphus, Eva Maria; Barth, Peter J. (December 2006). "The splenic marginal zone in humans and rodents: an enigmatic compartment and its inhabitants". Histochemistry and Cell Biology. 126 (6): 641–648. doi:10.1007/s00418-006-0210-5. PMID 16816939. S2CID 31943597.
- Martin, Flavius; Kearney, John F. (May 2002). "Marginal-zone B cells". Nature Reviews Immunology. 2 (5): 323–35. doi:10.1038/nri799. PMID 12033738. S2CID 22573840.
- den Haan, Joke M.M.; Kraal, Georg (2012). "Innate Immune Functions of Macrophage Subpopulations in the Spleen". Journal of Innate Immunity. 4 (5–6): 437–445. doi:10.1159/000335216. ISSN 1662-8128. PMC 6741446. PMID 22327291.
- Pillai S, Cariappa A, Moran ST (2005). "Marginal zone B cells". Annual Review of Immunology. 23: 161–96. doi:10.1146/annurev.immunol.23.021704.115728. PMID 15771569.
- Ferguson AR, Corley RB (2005). "Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-κB p50-deficient mice". BMC Immunology. 6: 8. doi:10.1186/1471-2172-6-8. PMC 1087843. PMID 15836790.
- Marginal zone lymphomas
- Song H, Cerny J (December 2003). "Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen". The Journal of Experimental Medicine. 198 (12): 1923–35. doi:10.1084/jem.20031498. PMC 2194154. PMID 14662910.
- Kraal G (1992). Cells in the marginal zone of the spleen. International Review of Cytology. 132. pp. 31–74. doi:10.1016/S0074-7696(08)62453-5. ISBN 9780123645326. PMID 1555921.
- Kumararatne DS, MacLennan IC (November 1981). "Cells of the marginal zone of the spleen are lymphocytes derived from recirculating precursors". European Journal of Immunology. 11 (11): 865–9. doi:10.1002/eji.1830111104. PMID 6976895. S2CID 22799132.