In Vivo Localisation Patterns and Cell-Cell Interactions of Cytokine Producing T-Cells and Specific Antibody Forming B-Cells
Because of its central position in the bloodstream and the large amount of migrating lymphocytes, the spleen plays a central role in the primary defense against bloodstream infections. Two critical functions of the spleen can be recognized: it serves as a large phagocytic filter and it is a major antibody producing organ1. Although the spleen participates significantly in host defense mechanisms, it is not essential for life. Nevertheless, its removal increases the risk on overwhelming infections by bacteria with polysaccharide capsules, e.g. Streptococcus pneumonia, Neisseria meningitidis orHaemo-philus influenza 2. After primary i.v. immunization, the spleen is the major site of antibody production3. Since eight times more lymphocytes recirculate via the spleen than via all lymph nodes together4, it is most likely that the entire antigen-specific B- T-cell repertoire is available in the spleen. The complex anatomical organization of the spleen with distinct compartments containing specialized cell types provides a unique micro-environment allowing cell-cell interactions which are essential for the initiation and continuation of various immune responses5 (fig. 1). To fully understand the role of the spleen in the immune response it is obviously necessary to look at this organ in a functional in vivo way. This means that one should switch from conventional phenotyping of immunocompetent cells to a more functional characterisation (e.g. resting vs activated). In looking at B-cells one should for example clearly separate membrane-Ig positive, memory and plasma cells. The latter group can be further subdivided by looking at the antigen specificity of the produced antibodies. For this purpose we developed new methodology for the detection of antigen specific antibody forming B-cells (AFCs) in tissue sections. By double staining we could also simultaneously determine the isotype of these AFCs (reviewed in: 6).
KeywordsMigration Pneumonia Influenza Polysaccharide Dextran
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- 2.E. Claassen,, A. Ott, C.D. Dijkstra, W.J.A. Boersma, C. Deen, N. Kors, M.M. Schellekens, and N. Van Rooijen. 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. 77:445 (1989).PubMedGoogle Scholar
- 6.E. Claassen, K. Gerritse, J.D. Laman, W.J.A. Boersma. New immuno-enzyme-cytochemical stainings for the in situ detection of epitope specificity and isotype of antibody forming B-cells in experimental and natural (auto)immune responses in animals and man, J. Immunol. Methods 150:207 (1992).PubMedCrossRefGoogle Scholar
- 8.E. Claassen, Q. Vos, A. Ott, M.M. Schellekens, W.J.A. Boersma. Role of the splenic marginal zone in the removal of, and immune response against, neutral polysaccharides, in: Lympathic Tissues and In Vivo Immune Responses, B. Imhof, S. Berrih-Aknin, S. Ezine, ed., Marcel Dekker, New York, (1991).Google Scholar
- 15.A.J.M. Van den Eertwegh, R.J. Noelle, M. Roy, D.M. Shepherd, A. Aruffo, J.A. Ledbetter, W.J.A Boersma and E. Claassen. In vivo CD40-gp39 interactions are essential for thymus dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines and antibody production delineates sites of cognate T-B cell interactions, J. Exp. Med. 178:xxx (1993).Google Scholar
- 18.A.J.M. Van den Eertwegh, M.J. Fasbender, W.J.A. Boersma and E. Claassen. In vivo detection, kinetics and characterization of interferon-gamma producing cells during a thymus dependent immune response: an immunohistochemical study, in: Lymphatic Tissues and In Vivo Immune Responses, B. Imhof, S. Berrih-Aknin, and S. Ezine, ed., Marcel Dekker Inc., New York (1991).Google Scholar
- 19.A.J.M. Van den Eertwegh, M.J. Fasbender, M.M. Schellekens, A. Van Oudenaren, W.J.A. Boersma and E. Claassen. In vivo kinetics and characterization of IFN-γproducing cells during a thymus independent immune response, J. of Immunol. 147:439 (1991).Google Scholar
- 23.A.J.M. Van den Eertwegh, S. Ganesh, W.J.A. Boersma, and E. Claassen. In vivo activity of cells with different cytokine profile after immunization with an antibody to IgD, in: Cytokines: Basic Principles and Clinical Applications, S. Romagnani, T.R. Mosmann, and A.K. Abbas, ed., Raven press, New York (1992).Google Scholar
- 26.F.D. Finkelman, D.K. Goroff, M. Fultz, S.C. Morris, J.M. Holmes, and J.J. Mond. Polyclonal activation of the murine immune system by an antibody to IgD; X. Evidence that the Precursors of IgGl-secreting cells are newly generated membrane IgD+ B cells rather than the B cells that are initially activated by anti-IgD antibody, J. Immunol 145:3562 (1990).PubMedGoogle Scholar