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

Figure 1.

Schematic drawing of a longitudinal section through the rat splenic white pulp. The (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 (GC), the (CO) and the marginal zone (MZ) are B‐cell regions. PALS, germinal centre and corona are separated from the marginal zone by the (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 . 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 (PFZ) are hypothetical: (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 . 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 (mAb) L26. Four distinct compartments are revealed: the (gc) appears light due to the presence of unstained CD4+ T cells and follicular dendritic cells. (co) is populated by smaller cells and stains more darkly because of the nuclear counterstain. The (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 (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. (ABC) technique on paraffin section, (DAB) chromogen. Bar, 80 μm. (b) Detection of smooth muscle alpha actin by mAb asm‐1 in a paraffin section. A row of actin‐positive fibroblasts divides the (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 μm. (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 μm. (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 μm. Reproduced with permission from Steiniger and Barth . Copyright © 2000 Springer.



Bajenoff M, Glaichenhaus N and Germain RN (2008) Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone. Journal of Immunology 181: 3947–3954.

Dijkstra CD, Döpp EA, Joling P and Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies. Immunology 54: 589–599.

Di Sabatino A, Carsetti R and Corazza GR (2011) Post‐splenectomy and hyposplenic states. Lancet 387: 86–97.

Funk EM, Heidemann P, Bolkenius M and Witte J (1997b) Standortbestimmung der Impf‐ und Antibioticaprophylaxe bei Splenektomie Teil II: Kinder. Chirurg 68: 591–595.

Funk EM, Schlimok G, Ehret W and Witte J (1997a) Standortbestimmung der Impf‐ und Antibioticaprophylaxe bei Splenektomie Teil I: Erwachsene. Chirurg 68: 586–590.

Hammerschmidt SI, Ahrendt M, Bode U et al. (2008) Stromal mesenteric lymph node cells are essential for the generation of gut‐homing T cells in vivo. Journal of Experimental Medicine 205: 2483–2490.

Klein U, Rajewsky K and Küppers R (1998) Human immunoglobulin (Ig) M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. Journal of Experimental Medicine 188: 1679–1689.

Kraal G (1992) Cells in the marginal zone of the spleen. International Reviews of Cytology 132: 31–74.

Kruetzmann S, Rosado MM, Weber H et al. (2003) Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. Journal of Experimental Medicine 197: 939–945.

MacLennan ICM, Gulbranson‐Judge A, Toellner K‐M et al. (1997) The changing preference of T and B cells for partners as T‐dependent antibody responses develop. Immunological Reviews 156: 53–66.

Matsuno K, Ezaki T and Kotani M (1989) Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen‐laden marginal metallophils and ED2‐positive macrophages in the rat. Cell and Tissue Research 257: 459–470.

Pack M, Trumpfheller C, Thomas D et al. (2008) DEC‐205/CD205+ dendritic cells are abundant in the white pulp of the human spleen, including the border region between the red and white pulp. Immunology 123: 438–446.

Phan TG, Green JA, Gray EE et al. (2009) Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nature Immunology 10: 786–793.

Roozendaal R and Mebius RE (2011) Stromal cell–immune cell interactions. Annual Reviews in Immunology 29: 23–43.

Shatz DV (2002) Vaccination practices among North American trauma surgeons in splenectomy for trauma. Journal of Trauma Injury, Infection, and Critical Care 53: 950–956.

Shaw JHF and Print CG (1989) Postsplenectomy sepsis. British Journal of Surgery 76(10): 1074–1081.

Spencer J and Dogan A (2009) A common migratory highway between human spleen and mucosa‐associated lymphoid tissues; data from nature's own experiments. Mucosal Immunology 2: 380–382.

Steiniger B and Barth P (2000) Microanatomy and function of the spleen. Advances in Anatomy, Embryology and Cell Biology 151: 1–101.

Steiniger B, Barth P and Hellinger A (2001) The perifollicular and marginal zones of the human splenic white pulp. Do fibroblasts guide lymphocyte immigration? American Journal of Pathology 159: 501–512.

Steiniger B, Barth P, Herbst B et al. (1997) The species‐specific structure of microanatomical compartments in the human spleen: strongly sialoadhesin‐positive macrophages occur in the perifollicular zone, but not in the marginal zone. Immunology 92: 307–316.

Steiniger B, Bette M and Schwarzbach H (2011) The open microcirculation in human spleens: a three‐dimensional approach. Journal of Histochemistry and Cytochemistry 59: 639–648.

Steiniger B, Rüttinger L and Barth PJ (2003) The three‐dimensional structure of human splenic white pulp compartments. Journal of Histochemistry and Cytochemistry 51: 655–663.

Steiniger B, Stachniss V, Schwarzbach H and Barth PJ (2007) Phenotypic differences between red pulp capillary and sinusoidal endothelia help localizing the open splenic circulation in humans. Histochemistry and Cell Biology 128: 391–398.

Steiniger B, Timphus CM, Jacob R and Barth PJ (2005) CD27+ B cells in human lymphatic organs: re‐evaluating the splenic marginal zone. Immunology 116: 424–442.

Steiniger B, Timphus EM and Barth PJ (2006) The splenic marginal zone in humans and rodents – an enigmatic compartment and its inhabitants. Histochemistry and Cell Biology 126: 641–648.

Steinman RM, Pack M and Inaba K (1997) Dendritic cells in the T cell areas of lymphoid organs. Immunological Reviews 156: 25–37.

Timens W and Poppema S (1985) Lymphocyte compartments in human spleen. An immunohistologic study in normal spleens and noninvolved spleens in Hodgkin's disease. American Journal of Pathology 120: 443–454.

Van den Berg TK, Brevé JJP, Damoiseaux JGMC et al. (1992) Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule. Journal of Experimental Medicine 176: 647–655.

Van Krieken JHJM and te Velde J (1986) Immunohistology of the human spleen: an inventory of the localization of lymphocyte subpopulations. Histopathology 10: 285–294.

Van Krieken JHJM and te Velde J (1988) Normal histology of the human spleen. American Journal of Surgical Pathology 12: 777–785.

Van Rooijen N, Claassen E, Kraal G and Dijkstra CD (1989) Cytological basis of immune functions of the spleen. Immunocytochemical characterization of lymphoid and non‐lymphoid cells involved in the ‘in situ’ immune response. Progress in Histochemistry and Cytochemistry 19: 1–69.

Veerman AJP and van Ewijk W (1975) White pulp compartments in the spleen of rats and mice. A light and electron microscopic study of lymphoid and non‐lymphoid cell types in T‐ and B‐areas. Cell and Tissue Research 156: 417–441.

Victora GD, Schwickert TA, Fooksman DR et al. (2010) Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143: 592–605.

Weill JC, Weller S and Reynaud CA (2009) Human marginal zone B cells. Annual Reviews of Immunology 27: 267–285.

Weller S, Braun MC, Tan BK et al. (2004) Blood IgM ‘memory’ B cells are circulating splenic marginal zone B cells in humans. Blood 104: 3647–3654.

Further Reading

Mebius RE and Kraal G (2005) Structure and function of the spleen. Nature Reviews Immunology 5: 606–616.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Steiniger, Birte(Sep 2011) Spleen. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000900.pub3]