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. 1983 Nov 1;158(5):1522–1536. doi: 10.1084/jem.158.5.1522

The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs

PMCID: PMC2187139  PMID: 6355361

Abstract

The macrophage-specific antigen F4/80 has been localized in mouse lymphoid and hematopoietic tissue and skin using immunoperoxidase staining. The antigen permits identification of early mononuclear phagocyte precursors in the bone marrow, and is present also on larger cells forming the center of hematopoietic islands and lining vascular sinuses. In thymus F4/80+ cells are numerous in both cortex and medulla and are particularly concentrated around the corticomedullary region. In spleen, lymph node, and gut-associated lymphoid areas the major F4/80+ populations are in the red pulp, the medulla and subcapsular sinus, and the adjacent lamina propria, respectively. F4/80+ cells are rarely seen in T-dependent areas of lymph nodes, spleen, or Peyer's patch, but are present in large numbers in these areas during bacillus Calmette-Guerin (BCG)-induced inflammation. Macrophage infiltration occurs also in lymph nodes from athymic nu/nu mice and is therefore T cell independent. The interdigitating cell of T-dependent areas is F4/80-, but the Langerhans cell of the epidermis of the skin, which bears some ultrastructural resemblance to the interdigitating cell, is F4/80+. We conclude that the two cell types are probably not related.

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Selected References

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  1. Allen T. D., Potten C. S. Fine-structural identification and organization of the epidermal proliferative unit. J Cell Sci. 1974 Jul;15(2):291–319. doi: 10.1242/jcs.15.2.291. [DOI] [PubMed] [Google Scholar]
  2. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  3. Beller D. I., Unanue E. R. Thymic macrophages modulate one stage of T cell differentiation in vitro. J Immunol. 1978 Nov;121(5):1861–1864. [PubMed] [Google Scholar]
  4. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cline M. J., Golde D. W. Cellular interactions in haematopoiesis. Nature. 1979 Jan 18;277(5693):177–181. doi: 10.1038/277177a0. [DOI] [PubMed] [Google Scholar]
  6. Duijvestijn A. M., Hoefsmit E. C. Ultrastructure of the rat thymus: the micro-environment of T-lymphocyte maturation. Cell Tissue Res. 1981;218(2):279–292. doi: 10.1007/BF00210344. [DOI] [PubMed] [Google Scholar]
  7. Erb P., Stern A. C., Alkan S. S., Studer S., Zoumbou E., Gisler R. H. Characterization of accessory cells required for helper T cell induction in vitro: evidence for a phagocytic, Fc-receptor, and Ia-bearing cell type. J Immunol. 1980 Dec;125(6):2504–2507. [PubMed] [Google Scholar]
  8. Ezekowitz R. A., Austyn J., Stahl P. D., Gordon S. Surface properties of bacillus Calmette-Guérin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia. J Exp Med. 1981 Jul 1;154(1):60–76. doi: 10.1084/jem.154.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fossum S., Smith M. E., Bell E. B., Ford W. L. The architecture of rat lymph nodes. III. The lymph nodes and lymph-borne cells of the congenitally athymic nude rat (rnu). Scand J Immunol. 1980;12(5):421–432. doi: 10.1111/j.1365-3083.1980.tb00086.x. [DOI] [PubMed] [Google Scholar]
  10. Hirsch S., Austyn J. M., Gordon S. Expression of the macrophage-specific antigen F4/80 during differentiation of mouse bone marrow cells in culture. J Exp Med. 1981 Sep 1;154(3):713–725. doi: 10.1084/jem.154.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoefsmit E. C., Duijvestijn A. M., Kamperdijk E. W. Relation between langerhans cells, veiled cells, and interdigitating cells. Immunobiology. 1982 Apr;161(3-4):255–265. doi: 10.1016/S0171-2985(82)80081-8. [DOI] [PubMed] [Google Scholar]
  12. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  13. Hume D. A., Gordon S. Mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Identification of resident macrophages in renal medullary and cortical interstitium and the juxtaglomerular complex. J Exp Med. 1983 May 1;157(5):1704–1709. doi: 10.1084/jem.157.5.1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kamperdijk E. W., Raaymakers E. M., de Leeuw J. H., Hoefsmit E. C. Lymph node macrophages and reticulum cells in the immune response. I. The primary response to paratyphoid vaccine. Cell Tissue Res. 1978 Aug 25;192(1):1–23. doi: 10.1007/BF00231019. [DOI] [PubMed] [Google Scholar]
  15. Kelly R. H., Balfour B. M., Armstrong J. A., Griffiths S. Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells. Anat Rec. 1978 Jan;190(1):5–21. doi: 10.1002/ar.1091900103. [DOI] [PubMed] [Google Scholar]
  16. Kelly R. H. Localization of afferent lymph cells within the draining node during a primary immune response. Nature. 1970 Aug 1;227(5257):510–513. doi: 10.1038/227510a0. [DOI] [PubMed] [Google Scholar]
  17. Kotani M., Okada K., Fujii H., Tsuchiya H., Matsuno K., Ekino S., Fukuda S. Lymph macrophages enter the germinal center of lymph nodes of guinea pigs. Acta Anat (Basel) 1977;99(4):391–402. doi: 10.1159/000144862. [DOI] [PubMed] [Google Scholar]
  18. Kyewski B. A., Rouse R. V., Kaplan H. S. Thymocyte rosettes: multicellular complexes of lymphocytes and bone marrow-derived stromal cells in the mouse thymus. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5646–5650. doi: 10.1073/pnas.79.18.5646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LeFevre M. E., Hammer R., Joel D. D. Macrophages of the mammalian small intestine: a review. J Reticuloendothel Soc. 1979 Nov;26(5):553–573. [PubMed] [Google Scholar]
  20. Mayrhofer G., Pugh C. W., Barclay A. N. The distribution, ontogeny and origin in the rat of Ia-positive cells with dendritic morphology and of Ia antigen in epithelia, with special reference to the intestine. Eur J Immunol. 1983 Feb;13(2):112–122. doi: 10.1002/eji.1830130206. [DOI] [PubMed] [Google Scholar]
  21. Nadler P. I., Klingenstein R. J., Hodes R. J. Ontogeny of murine accessory cells: Ia antigen expression and accessory cell function in in vitro primary antibody responses. J Immunol. 1980 Aug;125(2):914–920. [PubMed] [Google Scholar]
  22. Niederhuber J. E. The role of I region gene products in macrophage - T lymphocyte interaction. Immunol Rev. 1978;40:28–52. doi: 10.1111/j.1600-065x.1978.tb00400.x. [DOI] [PubMed] [Google Scholar]
  23. Nussenzweig M. C., Steinman R. M., Unkeless J. C., Witmer M. D., Gutchinov B., Cohn Z. A. Studies of the cell surface of mouse dendritic cells and other leukocytes. J Exp Med. 1981 Jul 1;154(1):168–187. doi: 10.1084/jem.154.1.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nussenzweig M. C., Steinman R. M., Witmer M. D., Gutchinov B. A monoclonal antibody specific for mouse dendritic cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):161–165. doi: 10.1073/pnas.79.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Persson U., Hammarström L., Möller E., Möller G., Smith C. I. The role of adherent cells in B and T lymphocyte activation. Immunol Rev. 1978;40:78–101. doi: 10.1111/j.1600-065x.1978.tb00402.x. [DOI] [PubMed] [Google Scholar]
  26. Pugh C. W., MacPherson G. G., Steer H. W. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983 Jun 1;157(6):1758–1779. doi: 10.1084/jem.157.6.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Remold-O'Donnell E. Biosynthesis of gp160, the major trypsin-sensitive surface glycoprotein of macrophages. J Biol Chem. 1982 Jun 10;257(11):6600–6604. [PubMed] [Google Scholar]
  28. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  29. Rowden G., Phillips T. M., Lewis M. G. Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscopic studies of surface antigens. Br J Dermatol. 1979 May;100(5):531–542. doi: 10.1111/j.1365-2133.1979.tb05578.x. [DOI] [PubMed] [Google Scholar]
  30. Schweizer J., Marks F. A developmental study of the distribution and frequency of Langerhans cells in relation to formation of patterning in mouse tail epidermis. J Invest Dermatol. 1977 Aug;69(2):198–204. doi: 10.1111/1523-1747.ep12506298. [DOI] [PubMed] [Google Scholar]
  31. Silberberg-Sinakin I., Gigli I., Baer R. L., Thorbecke G. J. Langerhans cells: role in contact hypersensitivity and relationship to lymphoid dendritic cells and to macrophages. Immunol Rev. 1980;53:203–232. doi: 10.1111/j.1600-065x.1980.tb01045.x. [DOI] [PubMed] [Google Scholar]
  32. Steinman R. M., Nussenzweig M. C. Dendritic cells: features and functions. Immunol Rev. 1980;53:127–147. doi: 10.1111/j.1600-065x.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
  33. Stingl G., Tamaki K., Katz S. I. Origin and function of epidermal Langerhans cells. Immunol Rev. 1980;53:149–174. doi: 10.1111/j.1600-065x.1980.tb01043.x. [DOI] [PubMed] [Google Scholar]
  34. Sunshine G. H., Katz D. R., Feldmann M. Dendritic cells induce T cell proliferation to synthetic antigens under Ir gene control. J Exp Med. 1980 Dec 1;152(6):1817–1822. doi: 10.1084/jem.152.6.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Veerman A. J. 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. 1974 Apr 11;148(2):247–257. doi: 10.1007/BF00224586. [DOI] [PubMed] [Google Scholar]
  36. Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976 Oct;186(2):161–184. doi: 10.1002/ar.1091860204. [DOI] [PubMed] [Google Scholar]
  37. Westen H., Bainton D. F. Association of alkaline-phosphatase-positive reticulum cells in bone marrow with granulocytic precursors. J Exp Med. 1979 Oct 1;150(4):919–937. doi: 10.1084/jem.150.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]

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