Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1997 Oct;92(2):307–316. doi: 10.1046/j.1365-2567.1997.00328.x

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.

B Steiniger 1, P Barth 1, B Herbst 1, A Hartnell 1, P R Crocker 1
PMCID: PMC1364073  PMID: 9415041

Abstract

The microanatomical structure of human and rat splenic white pulp is compared, with special emphasis on the localization of the marginal zone occupied by immunoglobulin M (IgM)+ IgD-/dull B lymphocytes and its specialized macrophages. Our study reveals that in contrast to rats, the marginal zone of humans primarily exists in the vicinity of primary and secondary splenic follicles and that it is almost absent around the periarteriolar T-cell zones. We demonstrate that in humans there is an additional compartment, the perifollicular zone, located between the marginal zone and the red pulp. The perifollicular zone is a dynamic region of variable cellular and phenotypic composition, which can be regarded either as a part of the red pulp or of the follicles. In most cases the perifollicular zone appears as a compartment of the red pulp containing erythrocyte-filled spaces which differ from the typical red pulp sinusoids. Similar to the splenic cords, the perifollicular zone mostly harbours scattered B and T lymphocytes. However, sometimes B lymphocytes clearly predominate in the perifollicular area. In addition, strongly sialoadhesin-positive macrophages form sheaths around capillaries in the perifollicular zone. Such capillary sheaths are not observed in rats. In humans weakly sialoadhesin-positive macrophages are also present in the perifollicular zone and in the red pulp. In some specimens sialoadhesin is, however, strongly expressed by a large number of dispersed perifollicular macrophages. Interestingly, in striking contrast to rats, the human marginal zone does not contain sialoadhesin-positive macrophages and marginal metallophilic macrophages are also absent in humans. Thus, sialoadhesin-positive macrophages and IgM+ IgD- memory B lymphocytes both share the marginal zone as a common compartment in rats, while they occupy different compartments in humans. We show that the human splenic marginal zone does not contain a marginal sinus and assume that in humans the perifollicular region is the compartment where antigen and recirculating lymphocytes enter the organ.

Full text

PDF
307

Images in this article

310Figure 1
on p.310
311Figure 2
on p.311
312Figure 3
on p.312

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brozman M. Anatomical pathways from the white to the red pulp in the human spleen. Acta Anat (Basel) 1985;121(3):189–193. doi: 10.1159/000145964. [DOI] [PubMed] [Google Scholar]
  2. Brozman M. Outer mantle zone of the follicle in the human spleen. Virchows Arch A Pathol Anat Histopathol. 1985;407(1):107–117. doi: 10.1007/BF00701333. [DOI] [PubMed] [Google Scholar]
  3. Buckley P. J. Phenotypic subpopulations of macrophages and dendritic cells in human spleen. Scanning Microsc. 1991 Mar;5(1):147–158. [PubMed] [Google Scholar]
  4. Crocker P. R., Mucklow S., Bouckson V., McWilliam A., Willis A. C., Gordon S., Milon G., Kelm S., Bradfield P. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J. 1994 Oct 3;13(19):4490–4503. doi: 10.1002/j.1460-2075.1994.tb06771.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Damoiseaux J. G., Döpp E. A., Dijkstra C. D. Cellular binding mechanism on rat macrophages for sialylated glycoconjugates, inhibited by the monoclonal antibody ED3. J Leukoc Biol. 1991 May;49(5):434–441. doi: 10.1002/jlb.49.5.434. [DOI] [PubMed] [Google Scholar]
  6. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  7. Dunn-Walters D. K., Isaacson P. G., Spencer J. Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells. J Exp Med. 1995 Aug 1;182(2):559–566. doi: 10.1084/jem.182.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hsu S. M. Phenotypic expression of B lymphocytes. III. Marginal zone B cells in the spleen are characterized by the expression of Tac and alkaline phosphatase. J Immunol. 1985 Jul;135(1):123–130. [PubMed] [Google Scholar]
  9. Humphrey J. H., Grennan D. Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal-zone macrophages. Eur J Immunol. 1981 Mar;11(3):221–228. doi: 10.1002/eji.1830110311. [DOI] [PubMed] [Google Scholar]
  10. Humphrey J. H. Tolerogenic or immunogenic activity of hapten-conjugated polysaccharides correlated with cellular localization. Eur J Immunol. 1981 Mar;11(3):212–220. doi: 10.1002/eji.1830110310. [DOI] [PubMed] [Google Scholar]
  11. Kraal G., Janse M. Marginal metallophilic cells of the mouse spleen identified by a monoclonal antibody. Immunology. 1986 Aug;58(4):665–669. [PMC free article] [PubMed] [Google Scholar]
  12. Kraal G., Ter Hart H., Meelhuizen C., Venneker G., Claassen E. Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody. Eur J Immunol. 1989 Apr;19(4):675–680. doi: 10.1002/eji.1830190416. [DOI] [PubMed] [Google Scholar]
  13. Kumararatne D. S., Bazin H., MacLennan I. C. Marginal zones: the major B cell compartment of rat spleens. Eur J Immunol. 1981 Nov;11(11):858–864. doi: 10.1002/eji.1830111103. [DOI] [PubMed] [Google Scholar]
  14. Li X. H., Paulus G., Atassi G., Buyssens N. Growth response of B16 melanoma to in vivo treatment with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) at the initial stage after tumor transplantation. Am J Pathol. 1984 Jun;115(3):403–411. [PMC free article] [PubMed] [Google Scholar]
  15. Liakka K. A., Autio-Harmainen H. I. Distribution of the extracellular matrix proteins tenascin, fibronectin, and vitronectin in fetal, infant, and adult human spleens. J Histochem Cytochem. 1992 Aug;40(8):1203–1210. doi: 10.1177/40.8.1377736. [DOI] [PubMed] [Google Scholar]
  16. Liu Y. J., Oldfield S., MacLennan I. C. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones. Eur J Immunol. 1988 Mar;18(3):355–362. doi: 10.1002/eji.1830180306. [DOI] [PubMed] [Google Scholar]
  17. Mason D. Y., Comans-Bitter W. M., Cordell J. L., Verhoeven M. A., van Dongen J. J. Antibody L26 recognizes an intracellular epitope on the B-cell-associated CD20 antigen. Am J Pathol. 1990 Jun;136(6):1215–1222. [PMC free article] [PubMed] [Google Scholar]
  18. Matsuno K., Ezaki T., Kotani M. Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophages in the rat. Cell Tissue Res. 1989 Sep;257(3):459–470. doi: 10.1007/BF00221456. [DOI] [PubMed] [Google Scholar]
  19. Radzun H. J., Hansmann M. L., Heidebrecht H. J., Bödewadt-Radzun S., Wacker H. H., Kreipe H., Lumbeck H., Hernandez C., Kuhn C., Parwaresch M. R. Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P. Lab Invest. 1991 Sep;65(3):306–315. [PubMed] [Google Scholar]
  20. SNOOK T. A comparative study of the vascular arrangements in mammalian spleens. Am J Anat. 1950 Jul;87(1):31–77. doi: 10.1002/aja.1000870103. [DOI] [PubMed] [Google Scholar]
  21. Saitoh K., Kamiyama R., Hatakeyama S. A scanning electron microscopic study of the boundary zone of the human spleen. Cell Tissue Res. 1982;222(3):655–665. doi: 10.1007/BF00213863. [DOI] [PubMed] [Google Scholar]
  22. Saitoh K., Kamiyama R., Hatakeyama S. A scanning electron microscopic study of the boundary zone of the human spleen. Cell Tissue Res. 1982;222(3):655–665. doi: 10.1007/BF00213863. [DOI] [PubMed] [Google Scholar]
  23. Schaffner A., Augustiny N., Otto R. C., Fehr J. The hypersplenic spleen. A contractile reservoir of granulocytes and platelets. Arch Intern Med. 1985 Apr;145(4):651–654. doi: 10.1001/archinte.145.4.651. [DOI] [PubMed] [Google Scholar]
  24. Schmidt E. E., MacDonald I. C., Groom A. C. Comparative aspects of splenic microcirculatory pathways in mammals: the region bordering the white pulp. Scanning Microsc. 1993 Jun;7(2):613–628. [PubMed] [Google Scholar]
  25. Schmidt E. E., MacDonald I. C., Groom A. C. Microcirculatory pathways in normal human spleen, demonstrated by scanning electron microscopy of corrosion casts. Am J Anat. 1988 Mar;181(3):253–266. doi: 10.1002/aja.1001810304. [DOI] [PubMed] [Google Scholar]
  26. Skalli O., Ropraz P., Trzeciak A., Benzonana G., Gillessen D., Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986 Dec;103(6 Pt 2):2787–2796. doi: 10.1083/jcb.103.6.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steiniger B., Klempnauer J., Wonigeit K. Phenotype and histological distribution of interstitial dendritic cells in the rat pancreas, liver, heart, and kidney. Transplantation. 1984 Aug;38(2):169–174. doi: 10.1097/00007890-198408000-00016. [DOI] [PubMed] [Google Scholar]
  28. Steiniger B., van der Meide P. H. High-dose interferon-gamma alters the distribution of B lymphocytes and macrophages in rat spleen and lymph nodes. Immunology. 1993 Mar;78(3):461–467. [PMC free article] [PubMed] [Google Scholar]
  29. Timens W., Boes A., Poppema S. Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation. Eur J Immunol. 1989 Nov;19(11):2163–2166. doi: 10.1002/eji.1830191129. [DOI] [PubMed] [Google Scholar]
  30. Timens W., Boes A., Rozeboom-Uiterwijk T., Poppema S. Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J Immunol. 1989 Nov 15;143(10):3200–3206. [PubMed] [Google Scholar]
  31. Timens W., Poppema S. Lymphocyte compartments in human spleen. An immunohistologic study in normal spleens and uninvolved spleens in Hodgkin's disease. Am J Pathol. 1985 Sep;120(3):443–454. [PMC free article] [PubMed] [Google Scholar]
  32. Timens W. The human spleen and the immune system: not just another lymphoid organ. Res Immunol. 1991 May;142(4):316–320. doi: 10.1016/0923-2494(91)90081-s. [DOI] [PubMed] [Google Scholar]
  33. Toccanier-Pelte M. F., Skalli O., Kapanci Y., Gabbiani G. Characterization of stromal cells with myoid features in lymph nodes and spleen in normal and pathologic conditions. Am J Pathol. 1987 Oct;129(1):109–118. [PMC free article] [PubMed] [Google Scholar]
  34. van Krieken J. H., Te Velde J., Kleiverda K., Leenheers-Binnendijk L., van de Velde C. J. The human spleen; a histological study in splenectomy specimens embedded in methylmethacrylate. Histopathology. 1985 Jun;9(6):571–585. doi: 10.1111/j.1365-2559.1985.tb02841.x. [DOI] [PubMed] [Google Scholar]
  35. van Krieken J. H., te Velde J. Immunohistology of the human spleen: an inventory of the localization of lymphocyte subpopulations. Histopathology. 1986 Mar;10(3):285–294. doi: 10.1111/j.1365-2559.1986.tb02482.x. [DOI] [PubMed] [Google Scholar]
  36. van Krieken J. H., te Velde J. Normal histology of the human spleen. Am J Surg Pathol. 1988 Oct;12(10):777–785. doi: 10.1097/00000478-198810000-00007. [DOI] [PubMed] [Google Scholar]
  37. van Vliet E., Melis M., van Ewijk W. Marginal zone macrophages in the mouse spleen identified by a monoclonal antibody. Anatomical correlation with a B cell subpopulation. J Histochem Cytochem. 1985 Jan;33(1):40–44. doi: 10.1177/33.1.3880783. [DOI] [PubMed] [Google Scholar]
  38. van den Berg T. K., Brevé J. J., Damoiseaux J. G., Döpp E. A., Kelm S., Crocker P. R., Dijkstra C. D., Kraal G. Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule. J Exp Med. 1992 Sep 1;176(3):647–655. doi: 10.1084/jem.176.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van den Berg T. K., van Die I., de Lavalette C. R., Döpp E. A., Smit L. D., van der Meide P. H., Tilders F. J., Crocker P. R., Dijkstra C. D. Regulation of sialoadhesin expression on rat macrophages. Induction by glucocorticoids and enhancement by IFN-beta, IFN-gamma, IL-4, and lipopolysaccharide. J Immunol. 1996 Oct 1;157(7):3130–3138. [PubMed] [Google Scholar]
  40. van den Berg T. K., van der Ende M., Döpp E. A., Kraal G., Dijkstra C. D. Localization of beta 1 integrins and their extracellular ligands in human lymphoid tissues. Am J Pathol. 1993 Oct;143(4):1098–1110. [PMC free article] [PubMed] [Google Scholar]
  41. van der Valk P., van der Loo E. M., Jansen J., Daha M. R., Meijer C. J. Analysis of lymphoid and dendritic cells in human lymph node, tonsil and spleen. A study using monoclonal and heterologous antibodies. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(2):169–185. doi: 10.1007/BF02889863. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES