Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1978 Apr 1;77(1):148–164. doi: 10.1083/jcb.77.1.148

Anatomy of germinal centers in mouse spleen, with special reference to "follicular dendritic cells"

PMCID: PMC2110033  PMID: 659510

Abstract

Lymphocyte proliferation in germinal centers (GC's) is thought to be triggered by antigen retained extracellularly on the surface of special "dendritic" cells. The anatomy and function of these cells have not been studied directly or in detail. We therefore examined mouse spleen GC's developing in response to sheep erythrocyte stimulation. We found that distincitve "follicular dendritic cells" (FDC's) were present in both the GC and adjacent mantle region of secondary follicles. The large, irregularly shaped nucleus, containing little heterochromatin, allowed for the light microscope (LM) identification of FDC's. By EM, the cell was stellate in shape sending out long, thin sheets of cytoplasm which could fold and coil into complex arrays. The processes were coated extracellularly by an amorphous electron-dense material of varying thickness, as well as particulates including variable numbers of virions. The FDC cytoplasm lacked organelles of active secretory and endocytic cells, such as well-developed rough endoplasmic reticulum (RER) and lysosomes. These anatomical features readily distinguished FDC's from other cell types, even those that were extended in shape. To pursue these descriptive findings, we injected three electron-dense tracers i.v. and sacrificed the mice 1 h-10 days thereafter. Colloidal carbon, colloidal thorium dioxide (cThO2), and soluble horseradish peroxidase (HRP) were actively sequestered into the vacuolar system of macrophages but were interiorized only in trace amounts by FDC's. Therefore, FDC's are not macrophages by cytologic and functional criteria. FDC's did display a unique property. Both colloidal carbon and thorium dioxide, which are nonimmunogens, could be visualized extracellularly on the cell surface for several days. The meaning of this is unclear, but the association of colloid with FDC's appeared to slow the movement of particulates through the extracellular space into the GC proper. FDC's were not readily identified in splenic white pulp lacking GC's. They must develop de novo then, possibly from novel dendritic cells that we have identified in vitro (Steinman, R. M., and Z. A. Cohn. 1973. J. Exp. Med. 137:1142-1162).

Full Text

The Full Text of this article is available as a PDF (6.2 MB).

Selected References

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

  1. Avrameas S., Taudou B., Chuilon S. Glutaraldehyde, cyanuric chloride and tetrazotized O-dianisidine as coupling reagents in the passive hemagglutination test. Immunochemistry. 1969 Jan;6(1):67–76. doi: 10.1016/0019-2791(69)90179-7. [DOI] [PubMed] [Google Scholar]
  2. Bianco C., Nussenzweig V. Complement receptors. Contemp Top Mol Immunol. 1977;6:145–176. doi: 10.1007/978-1-4684-2841-4_5. [DOI] [PubMed] [Google Scholar]
  3. Buerki H., Cottier H., Hess M. W., Laissue J., Stoner R. D. Distinctive medullary and germinal center proliferative patterns in mouse lymph nodes after regional primary and secondary stimulation with tetanus toxoid. J Immunol. 1974 Jun;112(6):1961–1970. [PubMed] [Google Scholar]
  4. Burke J. S., Simon G. T. Electron microscopy of the spleen. II. Phagocytosis of colloidal carbon. Am J Pathol. 1970 Jan;58(1):157–181. [PMC free article] [PubMed] [Google Scholar]
  5. Cohen S., Vassalli P., Benacerraf B., McCluskey R. T. The distribution of antigenic and nonantigenic compounds within draining lymph nodes. Lab Invest. 1966 Jul;15(7):1143–1155. [PubMed] [Google Scholar]
  6. FLIEDNER T., KESSE M., CRONKITE E. P., ROBERTSON J. S. CELL PROLIFERATION IN GERMINAL CENTERS OF THE RAT SPLEEN. Ann N Y Acad Sci. 1964 Feb 28;113:578–594. doi: 10.1111/j.1749-6632.1964.tb40692.x. [DOI] [PubMed] [Google Scholar]
  7. Hanna M. G., Jr, Szakal A. K. Localization of 125I-labeled antigen in germinal centers of mouse spleen: histologic and ultrastructural autoradiographic studies of the secondary immune reaction. J Immunol. 1968 Nov;101(5):949–962. [PubMed] [Google Scholar]
  8. Herd Z. L., Ada G. L. Distribution of 125I-immunoglobulins, IgG subunits and antigen-antibody complexes in rat lymph nodes. Aust J Exp Biol Med Sci. 1969 Feb;47(1):73–80. doi: 10.1038/icb.1969.6. [DOI] [PubMed] [Google Scholar]
  9. Howard J. C., Hunt S. V., Gowans J. L. Identification of marrow-derived and thymus-derived small lymphocytes in the lymphoid tissue and thoracic duct lymph of normal rats. J Exp Med. 1972 Feb 1;135(2):200–219. doi: 10.1084/jem.135.2.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MILLER J. J., 3rd, NOSSAL G. J. ANTIGENS IN IMMUNITY. VI. THE PHAGOCYTIC RETICULUM OF LYMPH NODE FOLLICLES. J Exp Med. 1964 Dec 1;120:1075–1086. doi: 10.1084/jem.120.6.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MOVAT H. Z., FERNANDO N. V. THE FINE STRUCTURE OF LYMPHOID TISSUE. Exp Mol Pathol. 1964 Dec;90:546–568. doi: 10.1016/0014-4800(64)90034-6. [DOI] [PubMed] [Google Scholar]
  12. Nieuwenhuis P., Ford W. L. Comparative migration of B- and T-Lymphocytes in the rat spleen and lymph nodes. Cell Immunol. 1976 May;23(2):254–267. doi: 10.1016/0008-8749(76)90191-x. [DOI] [PubMed] [Google Scholar]
  13. Nossal G. J., Abbot A., Mitchell J., Lummus Z. Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles. J Exp Med. 1968 Feb 1;127(2):277–290. doi: 10.1084/jem.127.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nossal G. J., Ada G. L., Austin C. M., Pye J. Antigens in immunity. 8. Localization of 125-I-labelled antigens in the secondary response. Immunology. 1965 Oct;9(4):349–357. [PMC free article] [PubMed] [Google Scholar]
  15. Nossal G. J., Austin C. M., Pye J., Mitchell J. Antigens in immunity. XII. Antigen trapping in the spleen. Int Arch Allergy Appl Immunol. 1966;29(4):368–383. [PubMed] [Google Scholar]
  16. ORTEGA L. G., MELLORS R. C. Cellular sites of formation of gamma globulin. J Exp Med. 1957 Nov 1;106(5):627–640. doi: 10.1084/jem.106.5.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Silverstein S. C., Steinman R. M., Cohn Z. A. Endocytosis. Annu Rev Biochem. 1977;46:669–722. doi: 10.1146/annurev.bi.46.070177.003321. [DOI] [PubMed] [Google Scholar]
  19. Sordat B., Sordat M., Hess M. W., Stoner R. D., Cottier H. Specific antibody within lymphoid germinal center cells of mice after primary immunization with horseradish peroxidase: a light and electron microscopic study. J Exp Med. 1970 Jan 1;131(1):77–91. doi: 10.1084/jem.131.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steinman R. M., Adams J. C., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen. J Exp Med. 1975 Apr 1;141(4):804–820. [PMC free article] [PubMed] [Google Scholar]
  21. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973 May 1;137(5):1142–1162. doi: 10.1084/jem.137.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steinman R. M., Lustig D. S., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo. J Exp Med. 1974 Jun 1;139(6):1431–1445. doi: 10.1084/jem.139.6.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Szakal A. K., Hanna M. G., Jr The ultrastructure of antigen localization and viruslike particles in mouse spleen germinal centers. Exp Mol Pathol. 1968 Feb;8(1):75–89. doi: 10.1016/0014-4800(68)90007-5. [DOI] [PubMed] [Google Scholar]
  24. WEISS L. THE WHITE PULP OF THE SPLEEN. THE RELATIONSHIPS OF ARTERIAL VESSELS, RETICULUM AND FREE CELLS IN THE PERIARTERIAL LYMPHATIC SHEATH. Bull Johns Hopkins Hosp. 1964 Aug;115:99–172. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES