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The development of the human lymph node

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Summary

Lymph nodes of human fetuses from the 11th to the 20th gestational week (g.w.) were investigated by light- and electron microscopy under particular consideration of the development of the T-cell and the B-cell regions and their specific reticulum cells. Lymph node development begins as a mesenchymal condensation, containing capillaries and mesenchymal cells; this primordium bulges into a lymph sac. Within the primordium of the lymph node granulopoiesis and erythropoiesis occur temporarily from the 12th to the 14th g.w. The first lymphoid cells and undifferentiated blast cells are seen in the 12th g.w.; monocytes and macrophages can be found from the 13th g.w. onward.

The development of the T-cell regions begins during the 13th g.w., before differentiation into cortex and medulla becomes obvious in the 14th g.w. Near the marginal sinus, cells displaying features of interdigitating reticulum cells (IDC) show similarities to monocytes. The morphological differentiation of the IDC is complete in the 17th g.w. when they are found in the paracortical region. Among the IDC, lymphoid cells with features of thymocytes are arranged in small groups.

The first indication of the development of B-cell regions can be recognized in the 14th g.w. when precursors of dendritic reticulum cells (DRC) are seen near the marginal sinus; this area also displays lymphoblasts, immunoblasts, and plasmoblasts. During the 20th g.w. small primary follicles are discernible in the outer cortex; in addition to blast cells they contain small lymphocytes, none of which show features of thymocytes. The morphological development of DRCs is not entirely complete until the 20th g.w.; however, some cells already show a characteristic network of interwoven processes.

The probable origin of (i) the IDC from monocytes, and (ii) the DRC and fibroblastic reticulum cells from a common type of mesenchymal precursor cells, as well as their significance for a specific micromilieu in the T-cell and the B-cell regions, are discussed.

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References

  • Ackermann GA (1967) Developmental relationship between the appearance of lymphocytes and lymphopoetic activity in the thymus and lymph nodes of the fetal cat. Anat Rec 158:387–400

    Google Scholar 

  • Bailey RP (1974) Occurrence and structure of postcapillary venules in human fetal lymph nodes. Anat Rec 178:302

    Google Scholar 

  • Bailey RP, Weiss L (1975a) Ontogeny of human fetal lymph nodes. Am J Anat 142:15–28

    Google Scholar 

  • Bailey RP, Weiss L (1975b) Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes. Am J Anat 143:43–58

    Google Scholar 

  • Bryant BJ (1974) The histo- and morphogenesis of lymph nodes: an interpretation of some mechanisms. J Reticuloendothel Soc 16:96–104

    Google Scholar 

  • Bryant BJ, Shifrine M (1972) Histogenesis of lymph nodes during development of the dog. J Reticuloendothel Soc 12:96–107

    Google Scholar 

  • Eikelenboom P, Nassy JJJ, Post J, Versteeg JCMB, Langevoort HL (1978) The histogenesis of lymph nodes in rat and rabbit. Anat Rec 190:201–216

    Google Scholar 

  • Ewijk W van, Verzijden JHM, van der Kwast THH, Luijcx-Meijer SWM (1974) Reconstitution of thymus dependent area in the spleen of lethally irradiated mice. Cell Tissue Res 149:43–60

    Google Scholar 

  • Frieß A (1976) Interdigitating reticulum cells in the popliteal lymph node of the rat. Cell Tissue Res 170:43–60

    Google Scholar 

  • Fukuda T (1973) Undifferentiated mononuclear cell in human embryonic liver; presumptive hemopoetic stem cell. Virch Arch B 14:31–34

    Google Scholar 

  • Fukuda T (1974) Fetal hemopoesis. II. Electron microscopic studies on human hepatic hemopoesis. Virch Arch B 16:249–270

    Google Scholar 

  • Furth Rvan, Schuit HRE, Hijmans W (1965) The immunological development of the human fetus. J Exp Med 122:1173–1188

    Google Scholar 

  • Gathings WE, Lawton AR, Cooper MD (1977) Immunofluorescent studies of the development of pre-Bcells B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol 7:804–810

    Google Scholar 

  • Gaudecker B von (1978) Ultrastructure of the age-involuted human thymus. Cell Tissue Res 186:507–525

    Google Scholar 

  • Gaudecker B von, Müller-Hermelink HK (1980) Ontogeny and organization of the stationary non-lymphoid cells in the human thymus. Cell Tissue Res 207:287–306

    Google Scholar 

  • Gaudecker B von, Müller-Hermelink HK (1982) 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 (Developments in hematology and immunology; V 3) Martinus Nijhoff Publishers. The Hague, Boston London, pp 51–58

    Google Scholar 

  • Gaudecker B von, Müller-Hermelink HK (1982 in press) The development of the human tonsilla palatina. Cell Tissue Res

  • Groscurth P (1980) Non-lymphatic cells in the lymph node cortex of the mouse. II. Postnatal development of the interdigitating cells and the dendritic reticular cells. Path Res Pract 169:235–254

    Google Scholar 

  • Heusermann U, Stutte HJ, Müller-Hermelink HK (1974) Interdigitating cells in the white pulp of the human spleen. Cell Tissue Res 153:415–417

    Google Scholar 

  • Hosteller JA, Ackermann GA (1969) Lymphopoiesis and lymph node histogenesis in the embryonic and neonatal rabbit. Am J Anat 124:57–75

    Google Scholar 

  • Kaiserling E, Lennert K (1974) Die interdigitierende Retikulumzelle der thymusabhängigen Region. Virch Arch B 16:51–61

    Google Scholar 

  • Kaiserling E, Stein H, Müller-Hermelink HK (1974) Interdigitating reticulum cell in the human thymus. Cell Tissue Res 155:47–55

    Google Scholar 

  • Kotani M, Nawa Y, Fujii H, Fukumoto T, Miyamato M, Yamashita A (1974) Postcapillary venules as the pathway for migrating B lymphocytes. Cell Tissue Res 252:299–303

    Google Scholar 

  • Lennert K, Niedorf HR (1969) Nachweis von desmosomal verknüpften Retikulumzellen im follikulären Lymphom (Brill Symmers). Virch Arch B 4:149–150

    Google Scholar 

  • Loke YW (1978) Development of immunocompetence in the human foetus. In: Loke YW (ed) Immunology and immunopathology of the human foetal-maternal interaction. Elsevier/North Holland Biomedical Press, Amsterdam New York Oxford, pp 51–61

    Google Scholar 

  • Matthes ML, Ax W, Fischer H (1971) Mikrokinematographische Studien für die Zellkooperation von Lymphocyten und Makrophagen nach primärem und sekundärem Stimulus mit löslichem Antigen. Z ges exp Med 154:253–264

    Google Scholar 

  • Milanesi S (1965) Sulla pesenza di dispositivi di giunzione tra le cellule dendritische dei follicoli linfatici del linfonodo. Boll Soc Ital Biol Sper 41:1223–1225

    Google Scholar 

  • Miller JJ, Nossal GJV (1964) Antigens in immunity. VI. The phagocytic reticulum cell of lymph node follicles. J Exp Med 120:1075–1086

    Google Scholar 

  • Mori Y, Lennert K (1969) Electronmicroscopic atlas of lymph node cytology and pathology. Springer Verlag, Berlin Heidelberg New York

    Google Scholar 

  • Mueller J, Brun del Re G, Bürki H, Keller HU, Hess MW, Cottier H (1975) Nonspecific esterase activity: a criterion for differentiation of T and B lymphocytes in mouse lymph nodes. Eur J Immunol 5:270–274

    Google Scholar 

  • Müller-Hermelink HK (1975) Herkunft der Lymphozyten und MikroÖkologie der lymphatischen Gewebe. Habilitationsschrift Kiel

  • Müller-Hermelink HK, Caesar R (1969) Elektronenmikroskopische Untersuchung der Keimzentren in menschlichen Tonsillen. Z Zellforsch 96:521–547

    Google Scholar 

  • Müller-Hermelink HK, Gaudecker B von (1980) Ontogenese des lymphatischen Systems beim Menschen (Referat). Verh Anat Ges 74:235–259

    Google Scholar 

  • Müller-Hermelink HK, Lennert K (1978) The cytologie, histologie, and functional bases for a modern classification of lymphomas. In: Lennert K (ed) Malignant lymphomas other the Hodgkin's disease. Handbuch der speziellen pathologischen Anatomie und Histologie, Bd 1/3 B. Hg Uehlinger E, Springer Verlag, Berlin Heidelberg New York, pp 1–82

    Google Scholar 

  • 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) Immuno reactivity of lymphocytes. Adv Exp Med Biol 66:177–182

  • Müller-Hermelink HK, Gaudecker B von, Drenckhahn D, Jaworsky K, Feldmann C (1981) Fibroblastic and dendritic reticulum cells of lymphoid tissue. — Ultrastructural, histochemical and 3H-thymidine labeling studies. J Cancer Res Clin Oncol 101:149–164

    Google Scholar 

  • Neta R, Salvin SB (1971) Cellular immunity in vitro: migration inhibition and phagocytosis. Infection and Immunity 4:697–702

    Google Scholar 

  • Nieuwenhuis P, Ford WL (1976) Comparative migration of B- and T-lymphocytes in the rat spleen and lymph nodes. Cell Immunol 23:254–267

    Google Scholar 

  • Nossal GJV, Abbot A, Mitchell J, Lummus Z (1968) Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles. J Exp Med 127:277–290

    Google Scholar 

  • Pernis B (1967) The immunoglobulins present in the germinal centers. In: Cottier H, Odartchenko N, Schindler R, Congdon CC (eds) Germinal centers in immune responses. Springer Verlag, Berlin Heidelberg New York, pp 112–119

    Google Scholar 

  • Rausch E, Kaiserling E, Goos M (1977) Langerhans cells and interdigitating reticulum cells in the thymus-dependent region in human dermatopathic lymphadenitis. Virch Arch B 25:327–343

    Google Scholar 

  • Richardson KG, Jarett L, Finke EH (1960) Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol 35:313–323

    CAS  PubMed  Google Scholar 

  • Silberberg-Sinakin I, Thorbecke GJ, Baer RL, Rosenthal SA, Berezowsky V (1976) Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell Immunol 25:137–151

    Google Scholar 

  • Silverberg-Sinakin I, Fedorko ME, Baer RL, Rosenthal SA, Berezowsky V, Thorbecke GJ (1977) Langerhans cells: target cells in immune complex reactions. Cell Immunol 32:400–416

    Google Scholar 

  • Silverstein AM, Lukes MD (1962) Fetal response to antigenetic stimulus. I. Plasmacellular and lymphoid reactions in the human fetus to intrauterine infections. Lab Invest 11:918–932

    Google Scholar 

  • Smyth AC, Weis L (1970) Electron microscopic study of inhibition of macrophage migration in delayed hypersensivity. J Immunol 105:1360–1375

    Google Scholar 

  • Sousa de M (1971) Kinetics of the distribution of thymus and marrow cells in the peripheral lymphoid organs of the mouse: ecotaxis. Clin Exp Immunol 9:371–380

    Google Scholar 

  • Stutte HJ, Müller-Hermelink HK (1976) Lysosomen in Blutzellen als diagnostischer Parameter. Verh dtsch Ges Path 60:155–175

    Google Scholar 

  • Swartzendruber DC (1965) Desmosomes in germinal centers of mouse spleen. Exp Cell Res 40:429–432

    Google Scholar 

  • Swartzendruber DC (1966) The fine structure of lymphatic tissue germinal centers. Reticular remnant after injury. Am J Path 48:613–626

    Google Scholar 

  • Swartzendruber DC (1967) Observations on the ultrastructure of lymphatic tissue germinal centers. In: Cottier H, Odartchenko N, Schindler R, Congdon CC (eds) Germinal centers in immune responses. Springer Verlag, Berlin Heidelberg New York, pp 71–76

    Google Scholar 

  • Veerman AJP (1974) On the interdigitating cells in the thymus-dependent area of the rat spleen: a relation between the mononuclear phagocyte system and T-lymphocytes. Cell Tissue Res 148:247–257

    Google Scholar 

  • Veldman JE (1970) Histophysiology and electron microscopy of the immune response. Ph D-Thesis, NV Boekdrukkerij Dijkstra Niemeyer, Groningen

    Google Scholar 

  • Veldman JE, Kaiserling E (1980) Interdigitating cells. In: Carr J, Daems WT (eds) The reticuloendothelial system, Vol I. Plenum Publishing Cooperation, pp 381–416

  • Veldman JE, Molenaar I, Keunig FJ (1978) Electron microscopy of cellular immunity reactions in B-cell deprived rabbits. Thymus derived antigen reactive cells, their microenvironment and progeny in the lymph node. Virch Arch B 28:217–228

    Google Scholar 

  • Watanabe Y, Tamaoki N, Habu S, Tashiro Y, Akatsuka S, Enomoto Y (1974) Fine structural study on human T- and B-lymphocytes (Engl. Abstr). Acta Haem Jpn 37:655–666

    Google Scholar 

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This investigation was supported by grants from the Deutsche Forschungsgemeinschaft and the Sonderforschungsbereich 111 of the Deutsche Forschungsgemeinschaft

The authors appreciate the contribution of human fetal material from Dr. J. von Hollweg and Dr. J. Körner, Hospital Heidberg, Hamburg, and the excellent technical assistance of Mrs. O.M. Bracker, Mrs. H. Hansen, Mrs. R. Köpke, Mrs. I. Knauer, Mrs. F. Müller, Mrs. H. Siebke, and Mrs. H. Waluk

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Markgraf, R., von Gaudecker, B. & Müller-Hermelink, H.K. The development of the human lymph node. Cell Tissue Res. 225, 387–413 (1982). https://doi.org/10.1007/BF00214691

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