Spleen

Birte Steiniger, University of Marburg, Marburg, Germany

Published online: September 2011

DOI: 10.1002/9780470015902.a0000900.pub3

Full Article on Wiley Online Library

The spleen is a secondary lymphoid organ present in all vertebrates, which monitors the blood. It consists of sessile stroma cells (fibroblasts), migratory cells of the immune system and blood-filled spaces and vessels. Splenic functions and microanatomy differ according to the species investigated. Certain functions such as immunological monitoring of bloodborne antigens, destruction of intravasal microorganisms and aged or abnormal blood cells, are more or less invariant. In rodents and humans the spleen is composed of two large compartments, the white pulp and the red pulp. The white pulp harbours dense accumulations of more or less migratory lymphocytes and antigen-presenting cells, which crawl on a meshwork of specialised fibroblasts. The red pulp is composed of connective tissue cords containing arterioles and capillaries and of sinuses, which represent a spleen-specific initial part of the venous circulation. The connective tissue of the red pulp cords is filled with blood and represents the only place where an open circulation occurs in the body. In addition, the cords harbour a dense population of specialised macrophages and some plasma cells. The article describes the microanatomical compartments of rat and human spleens, the course of B lymphocyte immune reactions in rodent spleens and the consequences of splenectomy in humans.

Key Concepts:

The spleen monitors the antigen composition of the blood.
The monitoring is predominantly carried out by lymphocytes recirculating through the spleen in the white pulp and by sessile macrophages in the red pulp cords.
Specialised fibroblasts recruit lymphocytes and macrophages to their compartments with the help of several mechanisms, such as secretion of chemokines or expression of certain adhesion molecules.
The splenic red pulp cords are the only location in the body with an open circulation. This means that blood flows in spaces not lined by any barrier-forming cells such as endothelia.
The open circulation thus permits a direct contact between the blood and resident macrophages.
In rodents and humans the spleen contains a special type of B lymphocytes, the marginal zone cells. These cells recognise polysaccharide antigens and are easily activated to become antibody-secreting plasma cells.
In humans, splenectomy leads to the loss of marginal zone-type B cells in the blood and to a reduced resistance against bacteria with polysaccharide capsules. This is especially relevant in children.
The susceptibility to overwhelming post-splenectomy infections in humans may be due to loss of the marginal zone and its special stromal cells in combination with loss of the large phagocyte compartment in the splenic red pulp.

Keywords: rat spleen; human spleen; white pulp compartments; red pulp; spleen function; splenectomy

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Article Title:	Spleen
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	Figure 1. Schematic drawing of a longitudinal section through the rat splenic white pulp. The central arteriole (CA) is accompanied by a broad periarteriolar lymphatic sheath (PALS) predominantly inhabited by T cells. The outer PALS (oPALS) also serves as a recirculation compartment for stimulated B cells. The germinal centre (GC), the corona/mantle zone (CO) and the marginal zone (MZ) are B-cell regions. PALS, germinal centre and corona are separated from the marginal zone by the marginal sinus (MS). The inset demonstrates that the inner wall of the marginal sinus is lined by marginal metallophilic macrophages whereas the outer wall is leaky and permits extravasation of particles and blood cells. The borderline separating the MZ from the red pulp does not exist and is only drawn for didactic reasons. Reproduced with permission from Steiniger and Barth (2000). Copyright © 2000 Springer.
	Figure 2. Schematic drawing of a longitudinal section through the human splenic white pulp. The central arteriole (CA) is accompanied by a relatively sparse periarteriolar lymphatic sheath (PALS). Germinal centre (GC), corona/mantle zone (CO) and marginal zone (MZ) represent B-cell regions. The marginal zone is subdivided by a shell of specialized fibroblasts (myofibroblasts, MF) into an inner marginal zone (iMZ) and an outer marginal zone (oMZ). The myofibroblasts are equivalent to fibroblastic reticulum cells (FRCs) of the PALS. Recent results indicate that the iMZ may be a recirculation compartment similar to the corona/mantle zone. The stippled area at the junction of fibroblasts (MF) and PALS indicates that CD4⁺ T cells may accompany the fibroblasts and that the fibroblasts continue into the outer PALS. The vascular structures in the perifollicular zone (PFZ) are hypothetical: sheathed capillaries (SC) and capillaries from the germinal centre may deliver their blood into open spaces. Distinct borders between corona and marginal zone and between marginal zone and perifollicular zone are absent due to lymphocyte migration. Borderlines are only depicted for didactic reasons. Capillaries and zones of the follicle are not drawn to scale. The ‘central arteriole’ may also traverse the corona/mantle zone or the germinal centre. Reproduced with permission from Steiniger and Barth (2000). Copyright © 2000 Springer.
	Figure 3. Peculiarities of the different zones of a secondary follicle in the human spleen. (a) Detection of B lymphocytes by staining of the CD20 surface antigen with monoclonal antibody (mAb) L26. Four distinct compartments are revealed: the germinal centre (gc) appears light due to the presence of unstained CD4⁺ T cells and follicular dendritic cells. The corona/mantle zone (co) is populated by smaller cells and stains more darkly because of the nuclear counterstain. The marginal zone (mz) is densely populated by larger CD20⁺ memory B cells with more cytoplasm and thus gives a paler impression. This area may not represent a separate compartment. The perifollicular zone (pfz) in this particular specimen harbours many CD20⁺ B cells intermingled with CD20^– monocytes and neutrophils. The large unstained areas in the perifollicular zone represent capillary sheaths. 15-year-old girl with splenic trauma. Avidin–biotin complex (ABC) technique on paraffin section, diaminobenzidine (DAB) chromogen. Bar, 80 m. (b) Detection of smooth muscle alpha actin by mAb asm-1 in a paraffin section. A row of actin-positive fibroblasts divides the inner marginal zone (imz) from the outer marginal zone. Typical appearance of a secondary follicle in healthy adults with a remnant of a germinal centre (gc) and a broad corona/mantle zone (co). The myofibroblasts correspond to FRCs and continue into the outer PALS at the right margin of the figure. 29-year-old female patient with splenic trauma. ABC technique, DAB chromogen. Bar, 50 m. (c) Sheathed capillaries demonstrated in the perifollicular zone (pfz) by strong staining with mAb HSN1 against human sialoadhesin (CD169) in a paraffin section. The capillary sheaths are closely associated with primary and secondary follicles and clearly occur outside the marginal zone (mz). They surround capillaries seemingly approaching the follicle from the red pulp, which branch in the perifollicular zone. (The CD169 staining in frozen sections is more widespread and also shows weak reactivity with red pulp macrophages.) gc and co indicate germinal centre and corona/mantle zone. Same specimen as in (a). ABC technique, DAB chromogen. Bar, 80 m. (d) Expression of CD15 in the perifollicular zone demonstrated by mAb 28. Monocytes and granulocytes are positive. These cells accumulate outside the clear marginal zone. The staining in the red pulp (right part of figure) is less dense. ABC technique on cryostat section. 53-year-old female patient with gastric malignancy. DAB chromogen. Bar, 100 m. Reproduced with permission from Steiniger and Barth (2000). Copyright © 2000 Springer.

Spleen

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