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Distribution of horseradish peroxidase (HRP)-anti-HRP immune complexes in mouse spleen with special reference to follicular dendritic cells.

The Journal of Cell Biology, 01 Oct 1978, 79(1):184-199
https://doi.org/10.1083/jcb.79.1.184 PMID: 701370 PMCID: PMC2110220

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Abstract 

The distribution of immune complexes has been studied in mouse spleen stimulated to contain many germinal centers (GC's). Horseradish peroxidase (HRP)-anti-HRP complexes were used as an appropriately precise and sensitive model. We were primarily interested in the relative abilities of three cell types to interact with complexes: lymphocytes, macrophages, and follicular dendritic cells (FDC's). The latter are distinctive, nonendocytic, stellate cells located primarily at the transition of mantle and GC zones of 2 degrees lymphoid follicles (Chen, L. L., J. C. Adams, and R. M. Steinman, 1978, J. Cell Biol. 77:148). Binding of immune complexes to lymphocytes could not be visualized in situ. Macrophages avidly interiorized complexes into lysosomes, but did not retain them extracellularly. In contrast, FDC's could retain HRP-anti-HRP extracellularly under appropriate conditions, but did not endocytose them. Cytochemical reactivity accumulated progressively on FDC's 1--6 h after administration of complexes i.v., remained stable in amount and location for 1 day, and then was progressively lost over a 1- to 5-day period. Several variables in the association of complexes with macrophages and FDC's were pursued. Only 1 microgram of complexed HRP had to be administered to visualize binding to both cell types. Macrophages interiorized complexes formed in a wide range of HRP/anti-HRP ratios, while FDC's associated with complexes formed in HRP excess only. Quantitative studies with [125I]HRP-anti-HRP demonstrated that 20% of the splenic load of HRP associated with FDC's. Complexes formed with an F(ab')2 anti-HRP were distributed primarily in macrophages. When the levels of the third component of serum complement were depleted by prior treatment with cobra venom factor, uptake of complexes by macrophages was reduced some 50% whereas association with FDC's was abolished. The fact that antigen excess complexes are retained extracellularly strengthens the idea that they are immunogenic. Finally, the association of complexes with FDC's seems to retard the entry of antigen into the GC proper.

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J Cell Biol. 1978 Oct 1; 79(1): 184–199.
PMCID: PMC2110220
PMID: 701370

Distribution of horseradish peroxidase (HRP)-anti-HRP immune complexes in mouse spleen with special reference to follicular dendritic cells

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Abstract

The distribution of immune complexes has been studied in mouse spleen stimulated to contain many germinal centers (GC's). Horseradish peroxidase (HRP)-anti-HRP complexes were used as an appropriately precise and sensitive model. We were primarily interested in the relative abilities of three cell types to interact with complexes: lymphocytes, macrophages, and follicular dendritic cells (FDC's). The latter are distinctive, nonendocytic, stellate cells located primarily at the transition of mantle and GC zones of 2 degrees lymphoid follicles (Chen, L. L., J. C. Adams, and R. M. Steinman, 1978, J. Cell Biol. 77:148). Binding of immune complexes to lymphocytes could not be visualized in situ. Macrophages avidly interiorized complexes into lysosomes, but did not retain them extracellularly. In contrast, FDC's could retain HRP-anti-HRP extracellularly under appropriate conditions, but did not endocytose them. Cytochemical reactivity accumulated progressively on FDC's 1--6 h after administration of complexes i.v., remained stable in amount and location for 1 day, and then was progressively lost over a 1- to 5-day period. Several variables in the association of complexes with macrophages and FDC's were pursued. Only 1 microgram of complexed HRP had to be administered to visualize binding to both cell types. Macrophages interiorized complexes formed in a wide range of HRP/anti-HRP ratios, while FDC's associated with complexes formed in HRP excess only. Quantitative studies with [125I]HRP-anti-HRP demonstrated that 20% of the splenic load of HRP associated with FDC's. Complexes formed with an F(ab')2 anti-HRP were distributed primarily in macrophages. When the levels of the third component of serum complement were depleted by prior treatment with cobra venom factor, uptake of complexes by macrophages was reduced some 50% whereas association with FDC's was abolished. The fact that antigen excess complexes are retained extracellularly strengthens the idea that they are immunogenic. Finally, the association of complexes with FDC's seems to retard the entry of antigen into the GC proper.

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Selected References

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  • Abrahams S, Phillips RA, Miller RG. Inhibition of the immune response by 7S antibody mechanism and site of action. J Exp Med. 1973 Apr 1;137(4):870–892. [Europe PMC free article] [Abstract] [Google Scholar]
  • Avrameas S, Leduc EH. Detection of simultaneous antibody synthesis in plasma cells and specialized lymphocytes in rabbit lymph nodes. J Exp Med. 1970 Jun 1;131(6):1137–1168. [Europe PMC free article] [Abstract] [Google Scholar]
  • BENACERRAF B, SEBESTYEN M, COOPER NS. The clearance of antigen antibody complexes from the blood by the reticuloendothelial system. J Immunol. 1959 Feb;82(2):131–137. [Abstract] [Google Scholar]
  • Bianco C, Nussenzweig V. Complement receptors. Contemp Top Mol Immunol. 1977;6:145–176. [Abstract] [Google Scholar]
  • Chen LL, Adams JC, Steinman RM. Anatomy of germinal centers in mouse spleen, with special reference to "follicular dendritic cells". J Cell Biol. 1978 Apr;77(1):148–164. [Europe PMC free article] [Abstract] [Google Scholar]
  • Czop J, Nussenzweig V. Studies on the mechanism of solubilization of immune precipitates by serum. J Exp Med. 1976 Mar 1;143(3):615–630. [Europe PMC free article] [Abstract] [Google Scholar]
  • Diener E, Feldmann M. Antibody-mediated suppression of the immune response in vitro. II. A new approach to the phenomenon of immunological tolerance. J Exp Med. 1970 Jul 1;132(1):31–43. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gajl-Peczalska KJ, Fish AJ, Meuwissen HJ, Frommel D, Good RA. Localization of immunological complexes fixing beta1C (C3) in germinal centers of lymph nodes. J Exp Med. 1969 Dec 1;130(6):1367–1393. [Europe PMC free article] [Abstract] [Google Scholar]
  • Graham RC, Jr, Karnovsky MJ. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. [Abstract] [Google Scholar]
  • Herd ZL, Ada GL. 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. [Abstract] [Google Scholar]
  • Howard JC, Hunt SV, Gowans JL. 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Laissue J, Cottier H, Hess MW, Stoner RD. Early and enhanced germinal center formation and antibody responses in mice after primary stimulation with antigen-isologous antibody complexes as compared with antigen alone. J Immunol. 1971 Sep;107(3):822–831. [Abstract] [Google Scholar]
  • Lang PG, Ada GL. Antigen in tissues. IV. The effect of antibody on the retention and localization of antigen in rat lymph nodes. Immunology. 1967 Nov;13(5):523–534. [Abstract] [Google Scholar]
  • Miller GW, Saluk PH, Nussenzweig V. Complement-dependent release of immune complexes from the lymphocyte membrane. J Exp Med. 1973 Sep 1;138(3):495–507. [Europe PMC free article] [Abstract] [Google Scholar]
  • Miller GW, Nussenzweig V. Complement as a regulator of interactions between immune complexes and cell membranes. J Immunol. 1974 Aug;113(2):464–469. [Abstract] [Google Scholar]
  • Nieuwenhuis P, Ford WL. Comparative migration of B- and T-Lymphocytes in the rat spleen and lymph nodes. Cell Immunol. 1976 May;23(2):254–267. [Abstract] [Google Scholar]
  • Nossal GJ, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nossal GJ, Austin CM, Pye J, Mitchell J. Antigens in immunity. XII. Antigen trapping in the spleen. Int Arch Allergy Appl Immunol. 1966;29(4):368–383. [Abstract] [Google Scholar]
  • OSTERLAND CK, HARBOE M, KUNKEL HG. Anti-gamma-globulin factors in human sera revealed by enzymatic splitting of anti-Rh antibodies. Vox Sang. 1963 Mar-Apr;8:133–152. [Abstract] [Google Scholar]
  • Papamichail M, Gutierrez C, Embling P, Johnson P, Holborow EJ, Pepys MB. Complement dependence of localisation of aggregated IgG in germinal centres. Scand J Immunol. 1975;4(4):343–347. [Abstract] [Google Scholar]
  • Ryan JL, Henkart PA. Fc receptor-mediated inhibition of murine B-lymphocyte activation. J Exp Med. 1976 Sep 1;144(3):768–775. [Europe PMC free article] [Abstract] [Google Scholar]
  • Sordat B, Sordat M, Hess MW, Stoner RD, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974 Feb 1;139(2):380–397. [Europe PMC free article] [Abstract] [Google Scholar]
  • Terashima K, Imai Y, Kasajima T, Tsunoda R, Takahashi K, Kojima M. An ultrastructure study on antibody production of the lymph nodes of rats with special reference to the role of germinal centers. Acta Pathol Jpn. 1977 Jan;27(1):1–24. [Abstract] [Google Scholar]
  • White RG, French VI, Stark JM. A study of the localisation of a protein antigen in the chicken spleen and its relation to the formation of germinal centres. J Med Microbiol. 1970 Feb;3(1):65–83. [Abstract] [Google Scholar]
  • White RG, Henderson DC, Eslami MB, Neilsen KH. Localization of a protein antigen in the chicken spleen. Effect of various manipulative procedures on the morphogenesis of the germinal centre. Immunology. 1975 Jan;28(1):1–21. [Abstract] [Google Scholar]
  • Williams RC, Jr, Lawrence TG., Jr Variations among gamma-globulins at the antigenic site revealed by pepsin digestion. J Clin Invest. 1966 May;45(5):714–723. [Europe PMC free article] [Abstract] [Google Scholar]
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