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.
B-Lymphocytes ; Cell Communication ; Dendritic Cells, Follicular* ; Fibroblasts ; Germinal Center ; Humans ; Immunity, Humoral ; Monocytes ; Palatine Tonsil ; Skin ; T-Lymphocytes

BACKGROUND: The molecular basis of follicular dendritic cells (FDC)-germinal center (GC) B cell interaction is largely unknown, although this cellular interaction is thought to be important for the whole process of GC B cell differentiation. METHODS: Using FDC-like cells, HK, and highly purified GC B cells, we attempted to identify the molecules that play critical roles in the interactions between FDC and B cells. GC B cells were co-cultured with HK cells and soluble CD154 in the presence or absence of various function-blocking monoclonal antibodies to examine their effect on GC B cell binding to HK cells and B cell proliferation. RESULTS: Anti-CD11a and anti-CD54 antibodies inhibited GC B cell binding to HK cells while anti-CD49d and anti-CD106 antibodies did not. GC B cell proliferation was not impaired by the disruption of GC B cell-HK cell adherence. CONCLUSION: Our results suggest that CD11a/CD18-CD54 interactions play an important roles in the initial binding of GC B cells to FDC and diffusible growth factors from FDC may be responsible the massive proliferation of GC B cells.
Antibodies ; Antibodies, Monoclonal ; B-Lymphocytes* ; Cell Communication ; Cell Differentiation ; Cell Proliferation ; Dendritic Cells, Follicular ; Germinal Center* ; Intercellular Signaling Peptides and Proteins

BACKGROUND: Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm consisting of heterogeneous cellular components and residual B-cell follicles. Because of such histological features, it is difficult to diagnose NMZL by fine needle aspiration (FNA) cytology. We reviewed FNA cytology of NMZL to identify a cytological clue to avoid misdiagnosing NMZL. METHODS: Histological, cytological, and clinical findings of seven cases of NMZL were reviewed. RESULTS: Most cases showed nodular aggregates of lymphohistiocytes derived from the germinal center irrespective of histological pattern. The cellular components were heterogeneous and composed of mature small lymphocytes, intermediate and large lymphocytes, immunoblasts, tingible body macrophages, and follicular dendritic cells. Intermediate-sized neoplastic cells with a pale nucleus were observed but difficult to identify because of admixed non-neoplastic cells, which outnumbered neoplastic cells. Except for one case with a high proportion of intermediate-sized cells, the other six cases were initially diagnosed as reactive hyperplasia. A flow cytometric analysis was performed in two cases and failed to demonstrate a monoclonal B-cell population. CONCLUSIONS: The FNA showing a reactive hyperplasia-like smear pattern should be carefully observed by experienced cytopathologists to identify intermediate-sized neoplastic cells. Clinical information including the size of the lymph nodes is important to avoid a misdiagnosis.
B-Lymphocytes ; Biopsy, Fine-Needle ; Dendritic Cells, Follicular ; Diagnostic Errors ; Germinal Center ; Hyperplasia ; Lymph Nodes ; Lymphocytes ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone ; Macrophages

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.
Apoptosis ; CD40 Ligand ; Cell Differentiation* ; Cell Line ; Cytokines ; Dendritic Cells, Follicular ; Germinal Center* ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Lymphoma ; Models, Theoretical ; Phenotype ; T-Lymphocytes

Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.
B-Lymphocytes ; Cytoplasm ; Dendritic Cells, Follicular* ; Focal Adhesion Protein-Tyrosine Kinases* ; Focal Adhesions* ; Germinal Center ; Humans* ; Lymphoid Tissue ; PDZ Domains ; Phosphorylation ; Proteins ; RNA, Small Interfering ; Syntenins*

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells of the immune system and these cells are essential for antigen presentation and regulation of the reactions in germinal centers. Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that shows a low-to-intermediate malignant potential. The most commonly involved sites are the lymph nodes, but FDCS may also occur at a variety of extranodal sites, including the oral cavity, tonsils, gastrointestinal tract and liver. We describe here a 79-year-old woman who had FDCS with extensive lymph node involvement, dry cough, and an itching sensation. The patient improved after systemic chemotherapy.
Aged ; Antigen Presentation ; Cough ; Dendritic Cell Sarcoma, Follicular ; Dendritic Cells ; Dendritic Cells, Follicular ; Female ; Gastrointestinal Tract ; Germinal Center ; Humans ; Immune System ; Liver ; Lymph Nodes ; Mouth ; Palatine Tonsil ; Pruritus ; Sensation

No abstract available.
Animals ; Erythrocytes* ; Germinal Center* ; Mice* ; Sheep* ; Spleen*

No abstract available.
Animals ; Germinal Center* ; Lymph Nodes* ; Mice*

OBJECTIVETo improve the understanding of progressive transformation of lymph node germinal centers (PTGC) and to explore its clinical, histopathologic and immunohistochemical features and the differential diagnosis between the related disease of germinal center hyperplasia.

METHODSThe clinical manifestation, laboratory bindings, treatment and outcome of a patient with PTGC were presented.

RESULTSThe main manifestation of the patient was painless peripheral lymphadenopathy. Histopathologic examination of an axillary lymph node showed reactive follicular hyperplasia and the progressive transformation changes germinal centers. The borderline between the germinal center and the mantle layer was obscured. The cells in the progressive transforming germinal centers were positive for CD20(+), CD5(+), CDw75(+).

CONCLUSIONPTGC is a rare lymphoid disorder. Histopathology and immunohistochemistry are important basis of the diagnosis.

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation (CD)8+ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.
Germinal Center ; Immune System Diseases ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory* ; Vaccines