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. 1996 Oct;64(10):4220–4225. doi: 10.1128/iai.64.10.4220-4225.1996

In vitro complement-dependent binding and in vivo kinetics of pneumococcal polysaccharide TI-2 antigens in the rat spleen marginal zone and follicle.

G Harms 1, M J Hardonk 1, W Timens 1
PMCID: PMC174359  PMID: 8926091

Abstract

For a better understanding of the spleen-dependent induction of the humoral immune response against thymus-independent type 2 antigens, we have studied the in vitro and in vivo localization of different capsular pneumococcal polysaccharides (PPSs) in the rat spleen. In this study, we found that in vitro binding of PPS types 3, 4, 6B, 9N/V, 14, and 23F was dependent on complement (probably a C3 fragment) and that the localization was predominantly restricted to the marginal-zone B lymphocytes and the follicular dendritic cells. In vivo, we observed with increase of time a shift of localized antigens. Shortly after injection, all PPS types localized in the marginal-zone B lymphocytes, then localized in the outer follicular mantle, and finally were found to be diffuse in the complete follicle and follicle corona. PPS types 3 and 9N/V and later also PPS type 23F localized additionally in red pulp macrophages. In particular, the localization in the marginal zone is important since the low flow in this area in combination with strongly CD21+ B cells, which are activated early, gives a maximum opportunity for the induction of a primary humoral immune response with subsequent differentiation into plasma cells or migration to the germinal center. In addition, the localization of PPSs at follicular dendritic cells should be considered important in the induction of an ongoing immune response not restricted to the spleen.

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Selected References

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  1. Claassen E., Kors N., Van Rooijen N. Influence of carriers on the development and localization of anti-trinitrophenyl antibody-forming cells in the murine spleen. Eur J Immunol. 1986 Mar;16(3):271–276. doi: 10.1002/eji.1830160311. [DOI] [PubMed] [Google Scholar]
  2. Claassen E., Kors N., van Rooijen N. Immunomodulation with liposomes: the immune response elicited by liposomes with entrapped dichloromethylene-diphosphonate and surface-associated antigen or hapten. Immunology. 1987 Apr;60(4):509–515. [PMC free article] [PubMed] [Google Scholar]
  3. Claassen E., Ott A., Boersma W. J., Deen C., Schellekens M. M., Dijkstra C. D., Kors N., Van Rooijen N. Marginal zone of the murine spleen in autotransplants: functional and histological observations in the response against a thymus-independent type 2 antigen. Clin Exp Immunol. 1989 Sep;77(3):445–451. [PMC free article] [PubMed] [Google Scholar]
  4. Claassen E., Westerhof Y., Versluis B., Kors N., Schellekens M., van Rooijen N. Effects of chronic injection of sphingomyelin-containing liposomes on lymphoid and non-lymphoid cells in the spleen. Transient suppression of marginal zone macrophages. Br J Exp Pathol. 1988 Dec;69(6):865–875. [PMC free article] [PubMed] [Google Scholar]
  5. Cohn D. A., Schiffman G. Immunoregulatory role of the spleen in antibody responses to pneumococcal polysaccharide antigens. Infect Immun. 1987 Jun;55(6):1375–1380. doi: 10.1128/iai.55.6.1375-1380.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  7. Griffioen A. W., Rijkers G. T., Janssens-Korpela P., Zegers B. J. Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2. Infect Immun. 1991 May;59(5):1839–1845. doi: 10.1128/iai.59.5.1839-1845.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Humphrey J. H. Splenic macrophages: antigen presenting cells for T1-2 antigens. Immunol Lett. 1985;11(3-4):149–152. doi: 10.1016/0165-2478(85)90161-0. [DOI] [PubMed] [Google Scholar]
  9. Humphrey J. H. Tolerogenic or immunogenic activity of hapten-conjugated polysaccharides correlated with cellular localization. Eur J Immunol. 1981 Mar;11(3):212–220. doi: 10.1002/eji.1830110310. [DOI] [PubMed] [Google Scholar]
  10. Jeurissen S. H., Dijkstra C. D. Characteristics and functional aspects of nonlymphoid cells in rat germinal centers, recognized by two monoclonal antibodies ED5 and ED6. Eur J Immunol. 1986 May;16(5):562–568. doi: 10.1002/eji.1830160518. [DOI] [PubMed] [Google Scholar]
  11. Kraal G., Ter Hart H., Meelhuizen C., Venneker G., Claassen E. Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody. Eur J Immunol. 1989 Apr;19(4):675–680. doi: 10.1002/eji.1830190416. [DOI] [PubMed] [Google Scholar]
  12. Kroese F. G., Timens W., Nieuwenhuis P. Germinal center reaction and B lymphocytes: morphology and function. Curr Top Pathol. 1990;84(Pt 1):103–148. doi: 10.1007/978-3-642-75519-4_5. [DOI] [PubMed] [Google Scholar]
  13. Kroese F. G., Wubbena A. S., Opstelten D., Deenen G. J., Schwander E. H., De Leij L., Vos H., Poppema S., Volberda J., Nieuwenhuis P. B lymphocyte differentiation in the rat: production and characterization of monoclonal antibodies to B lineage-associated antigens. Eur J Immunol. 1987 Jul;17(7):921–928. doi: 10.1002/eji.1830170705. [DOI] [PubMed] [Google Scholar]
  14. Lee C. J., Banks S. D., Li J. P. Virulence, immunity, and vaccine related to Streptococcus pneumoniae. Crit Rev Microbiol. 1991;18(2):89–114. doi: 10.3109/10408419109113510. [DOI] [PubMed] [Google Scholar]
  15. MacLennan I. C. Germinal centers. Annu Rev Immunol. 1994;12:117–139. doi: 10.1146/annurev.iy.12.040194.001001. [DOI] [PubMed] [Google Scholar]
  16. MacLennan I. C., Liu Y. J. Marginal zone B cells respond both to polysaccharide antigens and protein antigens. Res Immunol. 1991 May;142(4):346–351. doi: 10.1016/0923-2494(91)90089-2. [DOI] [PubMed] [Google Scholar]
  17. Markham R. B., Nicholson-Weller A., Schiffman G., Kasper D. L. The presence of sialic acid on two related bacterial polysaccharides determines the site of the primary immune response and the effect of complement depletion on the response in mice. J Immunol. 1982 Jun;128(6):2731–2733. [PubMed] [Google Scholar]
  18. Mathieson P. W., Qasim F. J., Thiru S., Oldroyd R. G., Oliveira D. B. Effects of decomplementation with cobra venom factor on experimental vasculitis. Clin Exp Immunol. 1994 Sep;97(3):474–477. doi: 10.1111/j.1365-2249.1994.tb06112.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Matsuno K., Ezaki T., Kotani M. Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophages in the rat. Cell Tissue Res. 1989 Sep;257(3):459–470. doi: 10.1007/BF00221456. [DOI] [PubMed] [Google Scholar]
  20. Matsuno K., Fujii H., Kotani M. Splenic marginal-zone macrophages and marginal metallophils in rats and mice. Cell Tissue Res. 1986;246(2):263–269. doi: 10.1007/BF00215888. [DOI] [PubMed] [Google Scholar]
  21. Mond J. J., Lees A., Snapper C. M. T cell-independent antigens type 2. Annu Rev Immunol. 1995;13:655–692. doi: 10.1146/annurev.iy.13.040195.003255. [DOI] [PubMed] [Google Scholar]
  22. Pepys M. B. Role of complement in induction of antibody production in vivo. Effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J Exp Med. 1974 Jul 1;140(1):126–145. doi: 10.1084/jem.140.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peset Llopis M. J., Harms G., Hardonk M. J., Timens W. Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells. J Allergy Clin Immunol. 1996 Apr;97(4):1015–1024. doi: 10.1016/s0091-6749(96)80078-9. [DOI] [PubMed] [Google Scholar]
  24. Rijkers G. T., Mosier D. E. Pneumococcal polysaccharides induce antibody formation by human B lymphocytes in vitro. J Immunol. 1985 Jul;135(1):1–4. [PubMed] [Google Scholar]
  25. Timens W., Boes A., Poppema S. Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation. Eur J Immunol. 1989 Nov;19(11):2163–2166. doi: 10.1002/eji.1830191129. [DOI] [PubMed] [Google Scholar]
  26. Timens W., Boes A., Vos H., Poppema S. Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells, medullary thymocytes, and peripheral T-cells. Histochemistry. 1991;95(6):605–611. doi: 10.1007/BF00266748. [DOI] [PubMed] [Google Scholar]
  27. Winkelstein J. A., Bocchini J. A., Jr, Schiffman G. The role of the capsular polysaccharide in the activation of the alternative pathway by the pneumococcus. J Immunol. 1976 Feb;116(2):367–370. [PubMed] [Google Scholar]
  28. van den Eertwegh A. J., Laman J. D., Schellekens M. M., Boersma W. J., Claassen E. Complement-mediated follicular localization of T-independent type-2 antigens: the role of marginal zone macrophages revisited. Eur J Immunol. 1992 Mar;22(3):719–726. doi: 10.1002/eji.1830220315. [DOI] [PubMed] [Google Scholar]

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