Cell and Tissue Research

, Volume 242, Issue 3, pp 579–592

The development of the human spleen

Ultrastructural studies in fetuses from the 14th to 24th week of gestation
  • Swantje Vellguth
  • Brita von Gaudecker
  • Hans-Konrad Müller-Hermelink
Article

Summary

Splenic tissue of human fetuses from the 14th to the 24th week of gestation (menstrual age) were investigated by light- and electron microscopy to describe the development of the red and white pulp in close relationship to the differentiation of the vascular tree. Special interest is focussed on the differentiation of the T-cell- and the B-cell regions and their specific stationary cells.

The preliminary stage, here called the “primary vascular reticulum,” lasts up to the 14th gestational week (gw). Numerous erythrocytes, normoblasts and macrophages are seen among a network of mesenchymal cells and argyrophilic fibers. Hematopoiesis, especially erythropoiesis, can be recognized.

The characteristic organ structure becomes established during the subsequent transformation stage of the fetal spleen, beginning with the 15th gw. Splenic lobules begin to form during the 15th to 17th gw. They consist of a central artery, surrounded by a sheath of lightly stained stationary cells which resemble myofibroblasts. At the periphery of these lobules the red pulp forms. Initially mobile cells are distributed throughout the reticulum. Soon they begin to accumulate in the venous sinuses, which develop from lacunae among the reticular network and come into contact with the venous system. The endothelial wall of these sinuses remains discontinuous, confirming the theory of the “open” vascularization of the spleen. The development of the larger veins is correlated with the differentiation of the splenic trabeculae.

The development of the white pulp is correlated with the stage of lymphoid colonization within the spleen, beginning around the 18th gw. An accumulation of lymphocytes around the central arteries can be recognized during the 19th and 20th gw. These lymphoid cells show morphological and immunohistochemical characteristics of T-precursor cells. Within the now assembling periarterial lymphoid sheath (PALS) a few precursors of interdigitating cells (IDC) are recognizable, giving evidence for the differentiation of the T-cell region.

Around the 23rd gw the assemblage of primary follicles is discernible at the periphery of the PALS. Precursors of the follicular dendritic reticulum cell (FDRC), the specific stationary cell of the B-cell region, have been recognized. This observation leads to the conclusion that the small primary follicles represent the beginning formation of the B-cell region.

The significance of the vascular system for the differentiation of the specific splenic organization is discussed.

Key words

Fetal human spleen Development Differentiation Red and white pulp T-cell regions B-cell regions 

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References

  1. De Bruyn P, Yongock Cho PH (1974) Contractile structures in endothelial cells of splenic sinusoids. J Ultrastruct Res 49:24–33Google Scholar
  2. Chen L, Weiss L (1972) Electron microscopy of the red pulp of human spleen. Am J Anat 134:425–458Google Scholar
  3. Ewijk W van, Verzijden JHM, Kwast ThH van der, Luijcx-Meijer SWM (1974) Reconstitution of thymus dependent area in the spleen of lethally irradiated mice. Cell Tissue Res 149:43–60Google Scholar
  4. Faller A, Martin R, Monney A (1977) Zur Frage der Entwicklung von Milzkapsel und Trabekelbaum und ihrer gegenseitigen Beziehungen an Hand zweier plastischer Modelle. Verh Anat Ges 71:765–769Google Scholar
  5. Fukuda T (1973a) Undifferentiated mononuclear cell in human embryonic liver; presumptive hemopoietic stem cell. Virchows Arch B 14:31–34Google Scholar
  6. Fukuda T (1973b) Fetal hemopoiesis. I. Electron microscopic studies on human yolk sac hemopoiesis. Virchows Arch B 14:197–213Google Scholar
  7. Fukuda T (1974) Fetal hemopoiesis. II. Electronmicroscopic studies on human hepatic hemopoiesis. Virchows Arch B 16:249–270Google Scholar
  8. Fukuda T (1981) Perifollicular, perisinusal and trabecular myofibroblasts in the human fetal spleen. Virchows Arch A 393:1–8Google Scholar
  9. Gaudecker B von, Müller-Hermelink HK (1980) Ontogeny and organization of the stationary non-lymphoid cells in the human thymus. Cell Tissue Res 207:287–306Google Scholar
  10. Gaudecker B von, Müller-Hermelink HK (1982a) Ultrastructural investigation of the lympho-epithelial and the lympho-mesenchymal interaction in the ontogeny of the human thymus. In: Fabris N (ed) Immunology and ageing. Martinus Nijhoff Publishers The Hague/Boston/London, pp 51–58Google Scholar
  11. Gaudecker B von, Müller-Hermelink HK (1982b) The development of the human tonsilla palatina. Cell Tissue Res 224:579–600Google Scholar
  12. Gaudecker B von, Müller-Hermelink HK (1985) Membranrezeptoren im lymphatischen System. 79. Verh Anat Ges (in press)Google Scholar
  13. Gaudecker B von, Pfingsten U, Müller-Hermelink HK (1984) Localization and characterization of T-cell-subpopulations and natural killer cells (HNK1+ cells) in the human tonsilla palatina: An ultrastructural-immunocytochemical study. Cell Tissue Res 238:135–143Google Scholar
  14. Gaudecker B von, Vellguth S, Müller-Hermelink HK (1985) Die Entwicklung der menschlichen Milz. Ultrastrukturelle und immunhistochemische Studien. 80. Verh Anat Ges (in press)Google Scholar
  15. Glauert AM, Glauert RH (1958) Araldite as an embedding medium for electron microscopy. J Biophys Biochem 4:191–194Google Scholar
  16. Helly K (1902) Zum Nachweis des geschlossenen Gefäßsystems der Milz. Arch Mikrosk Anat 59:93–105Google Scholar
  17. Herrath E von (1935) Bau und Funktion der Milz. Z Zellforsch 23:375–430Google Scholar
  18. Herrath E von (1939) Experimentelle Untersuchungen über die Beziehung zwischen Bau und Funktion der Sä ugermilz 1. Der Einfluß des Lauftrainings auf die Differenzierung der Milz heranwachsender Tiere b. Hunde. Z Mikrosk Anat Forsch, Leipzig 45:111–156Google Scholar
  19. Heusermann U, Stutte HJ (1974) Intercellular junctions of sinus lining cells in the human spleen. Cell Tissue Res 151:337–342Google Scholar
  20. Heusermann U, Stutte HJ (1975) Comparative histochemical and electron microscopic studies of the sinus and venous walls of the human spleen with special reference to the sinus-venous connections. Cell Tissue Res 163:519–533Google Scholar
  21. Heusermann U, Stutte HJ, Müller-Hermelink HK (1974) Interdigitating cells in the white pulp of the human spleen. Cell Tissue Res 153:415–417Google Scholar
  22. Heusermann U, Zurborn KH, Schroeder L, Stutte HJ (1980) The origin of the dendritic reticulum cell. An experimental enzymehistochemical and electron microscopic study on the rabbit spleen. Cell Tissue Res 209:279–294Google Scholar
  23. Irino S, Murakami T, Fujita T (1977) Open circulation in the human spleen. Dissection scanning electron microscopy of conductive-stained tissue and observation of resin vascular casts. Arch Histol Jpn 40:297–304Google Scholar
  24. Kaiserling E, Lennert K (1974) Die interdigitierende Retikulumzelle im menschlichen Lymphknoten — eine spezifische Zelle der thymusabhängigen Region. Virchows Arch B 16:51–61Google Scholar
  25. Kaiserling E, Stein H, Müller-Hermelink HK (1974) Interdigitating reticulum cells in the human thymus. Cell Tissue Res 155:47–55Google Scholar
  26. Knisely MH (1936) Spleen studies. I. Microscopic observation of the circulatory system of living unstimulated mammalian spleens. Anat Rec 65:23–50Google Scholar
  27. Knoll W (1929) Untersuchungen über embryonale Blutbildung beim Menschen. Z Mikrosk Anat Forsch 18:199–232Google Scholar
  28. Knoll W (1948) Der Gang der Embryogenese beim menschlichen Embryo. Schweiz Med Wochenschr 78:979Google Scholar
  29. Knoll W (1950) Die embryonale Blutbildung beim Menschen. Ber üb d Tätigkeit d St Gallischen Ges 73:1–100Google Scholar
  30. Laguesse E (1890) Recherches sur le développement de la rate chez les poissons. J Anat Physiol 26:345–425Google Scholar
  31. Ledbetter JA, Frankel AE, Herzenberg LA (1981) Human Leu T-Cell antigens: Quantitative expression on normal lymphoid cells and cell lines. In: Hämmerling G (ed) Monoclonal antibodies and T-cell hybridomas. North Holland New YorkGoogle Scholar
  32. Lennert K, Niedorf HR (1969) Nachweis von desmosomal verknüpften Retikulumzellen im follikulären Lymphom (Brill Symmers). Virchows Arch B 4:148–150Google Scholar
  33. Majno G (1979) The story of myofibroblasts. Am J Surg Pathol 3:535–542PubMedGoogle Scholar
  34. Majno G, Gabbiani G, Hirschel BJ, Ryan GB, Statkov PR (1971) Contraction of granulation tissue in vitro. Similarity to smooth muscle. Science 173:548–550Google Scholar
  35. Mall F (1898) The lobule of the spleen. J Hopkins Hosp Bull 218:219Google Scholar
  36. Markgraf R (1982) Die Lymphknotenentwicklung im menschlichen Feten unter besonderer Berücksichtigung der Differenzierung der T- und B-Zonen. Inauguraldissertation KielGoogle Scholar
  37. Markgraf R, Gaudecker B von, Müller-Hermelink HK (1982) The development of the human lymph node. Cell Tissue Res 225:387–413Google Scholar
  38. Martin R (1951) Milzkapsel und -balken. Z Anat Entw Gesch 116:96Google Scholar
  39. Mori Y, Lennert K (1969) Electron microscopic atlas of lymph node cytology and pathology. Springer, Berlin Heidelberg New YorkGoogle Scholar
  40. Movat HZ (1961) Silver impregnation methods for electron microscopy. Am J Clin Pathol 35:528–537Google Scholar
  41. Müller-Hermelink HK, Caesar R (1969) Elektronenmikroskopische Untersuchung der Keimzentren in menschlichen Tonsillen. Z Zellforsch 96:521–547Google Scholar
  42. Müller-Hermelink HK, Gaudecker B von (1980) Ontogenese des lymphatischen Systems beim Menschen (Referat). Verh Anat Ges 74:235–259Google Scholar
  43. Müller-Hermelink HK, Kaiserling E (1980) Different reticulum cells of the lymph node: microecological concept of lymphoid tissue organization. In: Tweel vd (ed) Malignant lymphoproliferative diseases. Martinus Nijhoff Publ. The Hauge Boston London, pp 57–70Google Scholar
  44. Müller-Hermelink HK, Lennert K (1978) The cytologic, histologic and functional bases for a modern classification of lymphomas. In: Lennert K (ed) Malignant lymphomas other than Hodgkin's diseases. Handbuch der speziellen pathologischen Anatomie und Histologie Bd I/3 B Hg Uehlinger ES 1–82 Springer, Berlin Heidelberg New York pp 1–71Google Scholar
  45. Müller-Hermelink HK, Heusermann U, Stutte HJ (1974) Enzyme histochemical obsevations on the localization and structure of the T cell and B cell regions in the human spleen. Cell Tissue Res 154:167–179Google Scholar
  46. Müller-Hermelink HK, Heusermann U, Kaiserling E, Stutte HJ (1976) Human lymphatic microecology-specifity, characterization and ontogeny of different reticulum cells in the B cell and T cell regions. In: Feldmann M, Globerson A (eds) Immune reactivity of lymphocytes. Adv Exp Med Biol 66:177–182Google Scholar
  47. Müller-Hermelink HK, Gaudecker B von, Drenckhahn D, Jaworsky K, Feldmann C (1981) Fibroblastic and dendritic reticulum cells of lymphoid tissue. J Cancer Res Clin Oncol 101:149–164Google Scholar
  48. Müller-Hermelink HK, Steinmann GG, Gaudecker B von (1982) Histogenesis of T cells. In: Goos M, Christophers E (eds) Lymphoproliferative diseases of the skin. Springer, Berlin Heidelberg New York, pp 16–24Google Scholar
  49. Ono K (1930) Untersuchungen über die Entwicklung der menschlichen Milz. Z Zellforsch mikr Anat 10:573–603Google Scholar
  50. Pabst R (1981) Die Milz, ein überflüssiges Organ? Med Klin 76:210–216Google Scholar
  51. Pawaresch MR, Radzun HJ, Hansmann ML, Peters KP (1983) Monoclonal antibody Ki-M4 specifically recognizes human dendritic reticulum cells (follicular dendritic cells) and their possible precursor in blood. Blood 62:585–590Google Scholar
  52. Pictet R, Orci L, Forssman WG, Girardier L (1969) An electron microscopic study of the perfusion-fixed spleen. I. The splenic circulation and the RES concept. Z Zellforsch 96:372–399Google Scholar
  53. Richardson KG, Jarett L, Finke EH (1960) Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol 35:313–323PubMedGoogle Scholar
  54. Saito H (1977) Fine structure of the reticular cells in the rat spleen, with special reference to their fibromuscular features. Arch Histol Jpn 40:333–345Google Scholar
  55. Saitoh K, Ryuichi K, Shigerue H (1982) A scanning electron microscopic study of the boundary zone of the human spleen. Cell Tissue Res 222:655–665Google Scholar
  56. Seifert K (1962) Zur Orientierung inhomogener Gewebeeinbettungen für die Ultramikrotomie. Mikroskopie 17:231–234Google Scholar
  57. Snook T (1975) The origin of the follicular capillaries in the human spleen. Am J Anat 144:113–117Google Scholar
  58. Snook KT (1980) The blood supply to the splenic lymphatic nodules in the rhesus monkey. Anat Rec 196:461–7Google Scholar
  59. Stutte HJ (1968) Nature of human spleen red pulp cells with special reference to sinus lining cells. Z Zellforsch 91:300–314Google Scholar
  60. Tischendorf F (1969) Die Milz. In: Handbuch der mikroskopischen Anatomie des Menschen, begr Möllendorf Wv, fortgef Bargmann W, Bd VI, Blutgefäß- und Lymphgefäßapparat, innersekretorische Drüsen. Springer, Berlin Heidelberg New YorkGoogle Scholar
  61. Veerman AJP (1974) On the interdigitating cells in the thymusdependent area of the rat spleen: a relation between the mononuclear phagocyte system and T-lymphocytes. Cell Tissue Res 148:247–257Google Scholar
  62. Veerman AJP (1975b) The postnatal development of the white pulp in the rat spleen and the onset of immunocompetence against a thymus-independent and a thymus-dependent antigen. Z Immunol Forsch 150:49–59Google Scholar
  63. Veerman AJP, Ewijk W van (1975a) 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 Tissue Res 156:417–441Google Scholar
  64. Veldman JE (1970) Histophysiology and electron microscopy of the immune response. Ph D Thesis, NV Boekdrukkerij Dijkstra Niemeyer GroningenGoogle Scholar
  65. Veldman JE, Kaiserling E (1980) Interdigitating cells. In: Carr J, Daems WT (eds) The reticuloendothelial system. Plenum Publ Comp New York, pp 381–415Google Scholar
  66. Venable JH, Coggeshall R (1965) A simplified lead citrate stain for use in electron microscopy. J Cell Biol 25:407–408CrossRefPubMedGoogle Scholar
  67. Weidenreich F (1901) Gefäßsystem der menschlichen Milz. Arch mikrosk Anat 58:247–376Google Scholar
  68. Weiss L (1973) The development of the primary vascular reticulum in the spleen of human fetuses (38 to 57 mm crown-rump length). Am J Anat 136:315–338Google Scholar
  69. Weiss L (1977) Histology Chapter 15: The spleen. In: Weiss L, Greep RO, Histology, Fourth Edition, pp 545–576Google Scholar
  70. Weiss L, Chen DT (1974) The differentiation of white pulp and red pulp in the spleen of human fetuses (72–145 mm crownrump length). Am J Anat 141:393–414Google Scholar
  71. Wiersborwsky A, Grouls V, Helpap B, Klingmüller G (1982) Electron-microscopic study of the development of the periarteriolar zone in splenic white pulp of rats. Cell Tissue Res 223:335–348Google Scholar
  72. Zwillenberg LO, Zwillenberg HHL (1963) Zur Struktur und Funktion der Hülsenkapillaren in der Milz. Z f Zellforsch 59:908–921Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Swantje Vellguth
    • 1
    • 2
  • Brita von Gaudecker
    • 1
    • 2
  • Hans-Konrad Müller-Hermelink
    • 1
    • 2
  1. 1.Anatomisches Institut der Universität KielKiel
  2. 2.Pathologisches Institut der Universität WürzburgLuitpold-KrankenhausBundesrepublik Deutschland
  3. 3.Anatomisches Institut der Universität KielKielGermany

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