Résumé
BACKGROUND: Follicular dendritic cells (FDCs) play key roles during T cell-dependent humoral immune responses by allowing antigen-specific B cells to survive, proliferate, and differentiate within the FDC networks of secondary follicles, i.e., germinal centers (GC). METHODS: A novel monoclonal antibody, 3C8, was generated by immunizing with an FDC line HK, in order to understand the molecular signals involved in the FDC-B cell interactions in the microenvironment of the GC. RESULTS: The 3C8 antibody did not bind to mononuclear cells, including T cells, B cells, and monocytes. Murine L929 and human skin fibroblasts exhibited no or little reactivity to 3C8. However, 3C8 specifically recognized HK cells by flowcytometry. Furthermore, the antigen recognized by 3C8 was restricted to the GC of the human tonsil. Dendritic networks of the GC were intensely stained by 3C8, but cells out side the GC were not. CONCLUSION: Our result s suggest that the antigen 3C8 may play some unique role on FDCs during the GC reactions.
Sujets)
Humains , Lymphocytes B , Communication cellulaire , Cellules dendritiques folliculaires , Fibroblastes , Centre germinatif , Immunité humorale , Monocytes , Tonsille palatine , Peau , Lymphocytes TRésumé
To delineate the individual role of follicular dendritic cells (FDC) and T cells at each stage of GC B cell differentiation at the clonal level and to analyze the signals required for the differentiation, we developed an experimental model using an FDC line, HK and a lymphoma cell line, L3055 for centroblasts. Phenotypic analysis of L 3055 revealed its origin of GC and the homogeneity. L3055 cells undergo spontaneous apoptosis when cultured in the absence of HK cells. L3055 cells proliferate continuously in the presence of HK cells, while they differentiate into a population with the phenotype of centrocytes after stimulation with CD40 ligand (CD 40L) plus IL-2, IL-4 and IL-10. L3055 undergo anti-Ig-mediated apoptosis, which is not protected by HK but by CD40L and the cytokines. These experimental results suggest that FDC provide signals for the survival and rapid proliferation of centroblasts and T cells trigger the differentiation of centroblasts into centrocytes.
Sujets)
Apoptose , Ligand de CD40 , Différenciation cellulaire , Lignée cellulaire , Cytokines , Cellules dendritiques folliculaires , Centre germinatif , Interleukine-10 , Interleukine-2 , Interleukine-4 , Lymphomes , Modèles théoriques , Phénotype , Lymphocytes TRésumé
No abstract available.