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. 1996 May 1;183(5):2367–2372. doi: 10.1084/jem.183.5.2367

Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling

PMCID: PMC2192569  PMID: 8642347

Abstract

Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study, we extended these observations by determining which TNF receptor (TNFR) is involved in morphological and functional differentiation of the spleen. Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the LT beta-receptor pathway, displayed an abnormal microarchitecture, and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. In this strain, immunofluorescence revealed a lack of follicular dendritic cells (FDC) network, detected with FDC-M1 as well as anti-CR1, and a lack of germinal centers, detected with peanut agglutinin. In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1.

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Selected References

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  1. Bachmann M. F., Kündig T. M., Hengartner H., Zinkernagel R. M. Regulation of IgG antibody titers by the amount persisting of immune-complexed antigen. Eur J Immunol. 1994 Oct;24(10):2567–2570. doi: 10.1002/eji.1830241046. [DOI] [PubMed] [Google Scholar]
  2. Banks T. A., Rouse B. T., Kerley M. K., Blair P. J., Godfrey V. L., Kuklin N. A., Bouley D. M., Thomas J., Kanangat S., Mucenski M. L. Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J Immunol. 1995 Aug 15;155(4):1685–1693. [PubMed] [Google Scholar]
  3. Beutler B., van Huffel C. Unraveling function in the TNF ligand and receptor families. Science. 1994 Apr 29;264(5159):667–668. doi: 10.1126/science.8171316. [DOI] [PubMed] [Google Scholar]
  4. Crowe P. D., VanArsdale T. L., Walter B. N., Ware C. F., Hession C., Ehrenfels B., Browning J. L., Din W. S., Goodwin R. G., Smith C. A. A lymphotoxin-beta-specific receptor. Science. 1994 Apr 29;264(5159):707–710. doi: 10.1126/science.8171323. [DOI] [PubMed] [Google Scholar]
  5. De Togni P., Goellner J., Ruddle N. H., Streeter P. R., Fick A., Mariathasan S., Smith S. C., Carlson R., Shornick L. P., Strauss-Schoenberger J. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994 Apr 29;264(5159):703–707. doi: 10.1126/science.8171322. [DOI] [PubMed] [Google Scholar]
  6. Dijkstra C. D., Kamperdijk E. W., Döpp E. A. The ontogenetic development of the follicular dendritic cell. An ultrastructural study by means of intravenously injected horseradish peroxidase (HRP)-anti-HRP complexes as marker. Cell Tissue Res. 1984;236(1):203–206. doi: 10.1007/BF00216532. [DOI] [PubMed] [Google Scholar]
  7. Erickson S. L., de Sauvage F. J., Kikly K., Carver-Moore K., Pitts-Meek S., Gillett N., Sheehan K. C., Schreiber R. D., Goeddel D. V., Moore M. W. Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature. 1994 Dec 8;372(6506):560–563. doi: 10.1038/372560a0. [DOI] [PubMed] [Google Scholar]
  8. Eugster H. P., Muller M., Karrer U., Car B. D., Schnyder B., Eng V. M., Woerly G., Le Hir M., di Padova F., Aguet M. Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice. Int Immunol. 1996 Jan;8(1):23–36. doi: 10.1093/intimm/8.1.23. [DOI] [PubMed] [Google Scholar]
  9. Gray D., Skarvall H. B-cell memory is short-lived in the absence of antigen. Nature. 1988 Nov 3;336(6194):70–73. doi: 10.1038/336070a0. [DOI] [PubMed] [Google Scholar]
  10. Groscurth P. Nicht-lymphatische Zellen in der Lymphknotenrinde der Maus. II. Postnatale Entwicklung der interdigitierenden Zellen und der dendritischen Retikulumzellen. Pathol Res Pract. 1980 Nov;169(3-4):235–254. doi: 10.1016/s0344-0338(80)80003-3. [DOI] [PubMed] [Google Scholar]
  11. Heinen E., Bosseloir A., Bouzahzah F. Follicular dendritic cells: origin and function. Curr Top Microbiol Immunol. 1995;201:15–47. doi: 10.1007/978-3-642-79603-6_2. [DOI] [PubMed] [Google Scholar]
  12. Heusermann U., Zurborn K. H., Schroeder L., Stutte H. J. The origin of the dendritic reticulum cell. An experimental enzyme-histochemical and electron microscopic study on the rabbit spleen. Cell Tissue Res. 1980;209(2):279–294. doi: 10.1007/BF00237632. [DOI] [PubMed] [Google Scholar]
  13. Kelly B. S., Levy J. G., Sikora L. The use of the enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of specific antibody from cell cultures. Immunology. 1979 May;37(1):45–52. [PMC free article] [PubMed] [Google Scholar]
  14. Kinoshita T., Takeda J., Hong K., Kozono H., Sakai H., Inoue K. Monoclonal antibodies to mouse complement receptor type 1 (CR1). Their use in a distribution study showing that mouse erythrocytes and platelets are CR1-negative. J Immunol. 1988 May 1;140(9):3066–3072. [PubMed] [Google Scholar]
  15. Klaus G. G., Humphrey J. H., Kunkl A., Dongworth D. W. The follicular dendritic cell: its role in antigen presentation in the generation of immunological memory. Immunol Rev. 1980;53:3–28. doi: 10.1111/j.1600-065x.1980.tb01038.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Pfeffer K., Matsuyama T., Kündig T. M., Wakeham A., Kishihara K., Shahinian A., Wiegmann K., Ohashi P. S., Krönke M., Mak T. W. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993 May 7;73(3):457–467. doi: 10.1016/0092-8674(93)90134-c. [DOI] [PubMed] [Google Scholar]
  18. Rothe J., Lesslauer W., Lötscher H., Lang Y., Koebel P., Köntgen F., Althage A., Zinkernagel R., Steinmetz M., Bluethmann H. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 1993 Aug 26;364(6440):798–802. doi: 10.1038/364798a0. [DOI] [PubMed] [Google Scholar]
  19. Szakal A. K., Kapasi Z. F., Haley S. T., Tew J. G. A theory of follicular dendritic cell origin. Curr Top Microbiol Immunol. 1995;201:1–13. doi: 10.1007/978-3-642-79603-6_1. [DOI] [PubMed] [Google Scholar]
  20. Tew J. G., Kosco M. H., Burton G. F., Szakal A. K. Follicular dendritic cells as accessory cells. Immunol Rev. 1990 Oct;117:185–211. doi: 10.1111/j.1600-065x.1990.tb00573.x. [DOI] [PubMed] [Google Scholar]
  21. Yoshida K., Kaji M., Takahashi T., van den Berg T. K., Dijkstra C. D. Host origin of follicular dendritic cells induced in the spleen of SCID mice after transfer of allogeneic lymphocytes. Immunology. 1995 Jan;84(1):117–126. [PMC free article] [PubMed] [Google Scholar]

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