Lokalisation follikulärer dendritischer Zellen (FDCs) bei Keimzentrumnsreaktionen in Tonsilla palatina und Milz bei Menschen

Follikuläre dendritische Zellen (FDCs) bilden die Grundstruktur der Follikel in allen sekundären lymphatischen Organen. Sie präsentieren langfristig auf ihren Fortsätzen gebundene Immunkomplexe und spielen eine wichtige Rolle für die Affinitätsreifung und den Isotypwechsel des Oberflächenimmunglo...

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Bibliographic Details
Main Author: Trabandt, Marc
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2010
Online Access:PDF Full Text
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Table of Contents: A meshwork of follicular dendritic cells (FDCs) forms the structure supporting Bcell follicles in all secondary lymphatic organs. FDCs confront follicular B-cells with immune complexes bound to their processes for prolonged periods. They play an important role for affinity maturation and isotype switching of surface immunoglobulin on germinal centre B-lymphocytes. In addition they contribute to the selection of B-lymphocytes by secreting pro- and anti-apoptotic mediators. FDCs are present in the entire follicle but their surface antigens differ in separate regions of germinal centres thus defining subpopulations of FDCs in humans and rodents. The present investigation characterizes FDCs by immunohistological detection of CD21, CD35 and CD23 and the antigen seen by monoclonal antibody CNA-42 in serial paraffin sections of human spleen and tonsil specimens. In addition, a so far unknown expression of some of these antigens in non-lymphatic tissues is described. Comparing the staining reactions permits to define phenotypically distinct zones within the follicles and to speculate about the dynamics of germinal centres in both organs. The immunhistological results presented lead to the following classification of follicles: Hyperplasic tonsils contain secondary follicles with and without an outer zone and, additionally, decaying follicles. Spleen specimens harbour secondary follicles with germinal centres involuting in an asymmetrical or symmetrical way. In addition follicles with extremely small remnants of germinal centres occur which resemble primary follicles but contain amyloid-like material. Others have described, that FDCs form five different zones in the secondary follicles of human tonsils. These zones are called dark zone, basal light zone, apical light zone, outer zone and corona or mantle zone. The investigation presented here permits to simultaneously visualize a maximum of four zones in a tonsil follicle. This is due to the fact, that not all zones are present in one and the same follicle. The outer zone, which is characterized by CD23- FDCs is absent in spleen specimens. It is, however, possible to define an inner marginal zone containing CD21+ FDCs at the surface of splenic follicles. This corresponds to the interpretation of others who have described the outer zone as a tonsil-specific compartment. The newly presented results do, however, show that the majority of follicles in hyperplastic tonsils lack an outer zone. This finding permits the conclusion, that the outer zone represents a stage-specific, but not an organspecific compartment of germinal centres. The germinal centres in hyperplastic tonsils appear to reach a stage of development that does not occur in the spleen of normal adults. The dynamics of secondary follicles in tonsils most likely differ decisively from those in other lymphatic organs. This is supported by the finding that germinal centres in tonsils appear to be acutely dissolved by focal apoptosis of FDCs and B-lymphocytes during an immune reaction. In contrast, germinal centres in spleen specimens of adults apparently shrink in a concentric way without exhibiting areas of apoptosis. Remnants of completely destroyed follicles do not occur in spleen specimens. The degenerated germinal centres in spleens resemble primary follicles by immunohistology. The majority of these follicles does, however, contain an amyloid-like material and an unusual distribution of CD23. This suggests that only minor B-cell reactions occur in normal spleens of adult patients and that degenerated secondary follicles may persist for prolonged periods. The number of FDC-defined histological zones in human secondary follicles thus depends on the stage of the ongoing B-cell reaction. The results presented show for the first time that germinal centres totally collapse during massive acute immune reactions instead of undergoing a slow involution. Immunohistological investigations of experimental germinal centre reactions in rodents might contribute to elucidate the mechanisms responsible for this phenomenon and their therapeutic value.