RESUMO
Germinal Centres (GCs) are transient structures in secondary lymphoid organs, where affinity maturation of B cells takes place following an infection. While GCs are responsible for protective antibody responses, dysregulated GC reactions are associated with autoimmune disease and B cell lymphoma. Typically, 'normal' GCs persist for a limited period of time and eventually undergo shutdown. In this review, we focus on an important but unanswered question - what causes the natural termination of the GC reaction? In murine experiments, lack of antigen, absence or constitutive T cell help leads to premature termination of the GC reaction. Consequently, our present understanding is limited to the idea that GCs are terminated due to a decrease in antigen access or changes in the nature of T cell help. However, there is no direct evidence on which biological signals are primarily responsible for natural termination of GCs and a mechanistic understanding is clearly lacking. We discuss the present understanding of the GC shutdown, from factors impacting GC dynamics to changes in cellular interactions/dynamics during the GC lifetime. We also address potential missing links and remaining questions in GC biology, to facilitate further studies to promote a better understanding of GC shutdown in infection and immune dysregulation.
Assuntos
Subpopulações de Linfócitos B/citologia , Centro Germinativo/citologia , Animais , Anticorpos/imunologia , Apresentação de Antígeno , Apoptose , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Divisão Celular , Linhagem da Célula , Citocinas/fisiologia , Células Dendríticas Foliculares/imunologia , Células Dendríticas Foliculares/ultraestrutura , Retroalimentação Fisiológica , Rearranjo Gênico do Linfócito B , Centro Germinativo/imunologia , Centro Germinativo/ultraestrutura , Humanos , Infecções/imunologia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfopoese , Macrófagos/imunologia , Células B de Memória/metabolismo , Camundongos , Modelos Imunológicos , Plasmócitos/citologia , Plasmócitos/imunologia , VacinasRESUMO
Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC neoplasm having features of follicular dendritic cells in a 54-year-old woman with right axillary lymph node swelling. The resected lymph node showed multiple nodular aggregations simulating and replacing normal follicles. The tumor cells had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin. They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the tumor cells had long interdigitating microvillus-like cell processes and oval to elongated vesicular nuclei. In addition, the intercellular spaces contained accumulations of collagen, and some tumor cells had desmosomal-like junctions. These findings suggest that the present case is a CK-positive FRC tumor with follicular dendritic cell features.
Assuntos
Biomarcadores Tumorais/análise , Células Dendríticas Foliculares , Transtornos Histiocíticos Malignos , Queratinas/análise , Linfonodos , Células Estromais , Biomarcadores Tumorais/genética , Biópsia , Células Dendríticas Foliculares/química , Células Dendríticas Foliculares/ultraestrutura , Feminino , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/patologia , Transtornos Histiocíticos Malignos/cirurgia , Humanos , Imuno-Histoquímica , Cariotipagem , Excisão de Linfonodo , Linfonodos/química , Linfonodos/cirurgia , Linfonodos/ultraestrutura , Microscopia Eletrônica , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Células Estromais/química , Células Estromais/ultraestrutura , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7-21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves.
Assuntos
Sistema Nervoso Entérico/metabolismo , Enterócitos/metabolismo , Nódulos Linfáticos Agregados/metabolismo , Doenças Priônicas/transmissão , Príons/metabolismo , Príons/patogenicidade , Animais , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/ultraestrutura , Endossomos/metabolismo , Endossomos/ultraestrutura , Sistema Nervoso Entérico/ultraestrutura , Enterócitos/ultraestrutura , Proteínas de Membrana Lisossomal/genética , Proteínas de Membrana Lisossomal/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Camundongos , Camundongos Knockout , Nódulos Linfáticos Agregados/ultraestrutura , Doenças Priônicas/genética , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Príons/genética , Transporte Proteico , Fatores de TempoRESUMO
BACKGROUND: Follicular dendritic cell (FDC) sarcoma is a rare low-to-intermediate grade malignant dendritic cell neoplasm that often has an indolent clinical course. FDC sarcomas are often misdiagnosed on aspiration cytology. CASE: A 26-year-old woman presented with a solid, slowly growing, painless mass in her right neck for 3 months. Computed tomography revealed a 3.6-cm, well-defined homogenous solid mass located posterior to the mandible and submandibular glands. Fine needle aspiration cytology revealed many large, spindle to ovoid epithelioid cells in singles, small clusters, and syncytial sheets with moderate to abundant cytoplasm, indistinct cell borders, irregular nuclear membrane, fine to vesicular chromatin, and conspicuous nucleoli. The background contained many small mature lymphocytes intimately mixed with large epithelioid tumor cells. Tumor cells were strongly positive for CD21, CD35, CD23, and fascin. Diagnosis of FDC sarcoma was rendered; follow-up surgical resection and ultrastructural study confirmed the diagnosis. The cytogenetic study showed a normal female karyotype 46,XX. CONCLUSION: Although the cytomorphology of FDC sarcoma is characteristic, a preoperative diagnosis of FDC sarcoma based on fine needle aspiration cytology is very challenging, if not impossible. Immunohistochemistry is always necessary for rendering and/or confirming the diagnosis, and ultrastructural studies are helpful.
Assuntos
Análise Citogenética , Sarcoma de Células Dendríticas Foliculares/genética , Sarcoma de Células Dendríticas Foliculares/patologia , Células Dendríticas Foliculares/patologia , Células Dendríticas Foliculares/ultraestrutura , Adulto , Biópsia por Agulha Fina , Proliferação de Células , Desmossomos/ultraestrutura , Humanos , Pescoço/patologiaRESUMO
Extranodal follicular dendritic cell sarcoma (FDCS) of the pharyngeal region is a rare malignant tumor recognized in recent years, with approximately 37 cases so far reported in the literature. It is often not considered at the initial evaluation and may be misdiagnosed in a small biopsy specimen. We report 4 cases of extranodal FDCS, 2 cases in the nasopharynx that were diagnosed as undifferentiated carcinomas because they were characterized by syncytial epithelial cells with sheet or nest-like distribution and 2 cases in the tonsil and soft palate that were characterized by vaguely concentric whorls consisting of spindle to ovoid cells. The latter case was diagnosed as ectopic meningioma. The analysis of all cases from the literature and ours shows that 58% (21/36) of the cases are misdiagnosed initially, often as undifferentiated carcinoma or meningioma, which the differential diagnoses should be mostly focused on. With a median follow-up of 27 months, the recurrence, metastasis, and mortality rates are 23%, 21%, and 3%, respectively, suggesting that extranodal FDCS of the pharyngeal region remains a low-grade sarcoma. Radical surgery is recommended, whereas there is no evidence to support adjuvant therapy.
Assuntos
Carcinoma/diagnóstico , Sarcoma de Células Dendríticas Foliculares/diagnóstico , Células Dendríticas Foliculares/ultraestrutura , Erros de Diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Biomarcadores Tumorais , DNA de Neoplasias/análise , Sarcoma de Células Dendríticas Foliculares/cirurgia , Intervalo Livre de Doença , Feminino , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d)) accumulations in the brain and lymphoreticular system (LRS). Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d) accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs) and tingible body macrophages (TBMs). Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs) of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d) plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d) accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d). Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d) accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.
Assuntos
Complexo Antígeno-Anticorpo/imunologia , Diferenciação Celular/imunologia , Células Dendríticas Foliculares/imunologia , Células Dendríticas Foliculares/patologia , Scrapie/imunologia , Scrapie/patologia , Animais , Complexo Antígeno-Anticorpo/ultraestrutura , Forma Celular , Células Dendríticas Foliculares/ultraestrutura , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Linfonodos/imunologia , Linfonodos/patologia , Linfonodos/ultraestrutura , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Proteínas PrPSc/metabolismo , Ubiquitina/metabolismoRESUMO
OBJECTIVE: To study the morphologic and immunophenotypic features of angioimmunoblastic T-cell lymphoma (AITL), as well as the origin of the proliferative follicular dendritic cells (FDCs) in AITL. METHODS: Immunohistochemical study for CD10, CXCL13, bcl-6 and CD21 was performed on 29 cases of AITL. Double immunostaining for bcl-6/CD3, CD10/CD21 and CD10/CD20 were also carried out. Cases of peripheral T-cell lymphoma, unspecified, extranodal NK/T-cell lymphoma, nasal-type, enteropathy-type T-cell lymphoma, anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma and reactive lymphoid proliferation were selected as controls. RESULTS: Amongst the 29 cases of AITL studied, 75.9% (22/29) showed aberrant expression of CD10, while all except one of the controlled cases were negative, 82.8% (24/29) of the AITL cases expressed CXCL13, while all cases of peripheral T-cell lymphoma, unspecified were negative. As for bcl-6 staining, although the highest percentage of bcl-6-positive cells was observed in AITL, the expression pattern was not useful in differentiating AITL from peripheral T-cell lymphoma, unspecified and lymphoid reaction. Besides, all cases of AITL demonstrated the characteristic proliferation of follicular dendritic cells. Two of the cases, which contained obvious germinal centers, had the follicular dendritic cell meshwork extending beyond the lymphoid follicles. CONCLUSIONS: As compared with bcl-6, CD10 and CXCL13 are specific and sensitive markers in diagnosing AITL. Part of the proliferative FDCs in AITL may originate from the germinal centers.
Assuntos
Quimiocina CXCL13/metabolismo , Células Dendríticas Foliculares/patologia , Linfadenopatia Imunoblástica/patologia , Linfoma de Células T Periférico/patologia , Neprilisina/metabolismo , Adulto , Idoso , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/ultraestrutura , Feminino , Humanos , Linfadenopatia Imunoblástica/metabolismo , Imunofenotipagem , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Receptores de Complemento 3d/metabolismoRESUMO
An antiserum against Eimeria tenella sporozoites was used to localize and isolate Ag-binding cells in intestinal cecal tonsils of parasite-infected chickens. Based on their tissue localization, ultrastructural features, and expression of surface markers, two subpopulations of cells were isolated, CD45(+) interdigitating dendritic cells (IDCs) and CD45(-) follicular dendritic cells (FDCs). IDCs expressed MHC class I, MHC class II, and selectin, induced the proliferation of allogeneic naïve CD4(+) T cells, and increased the secretion of IFN-gamma by autologous T cells. FDCs expressed surface IgG, IgM, ICAM-1, and VCAM-1, stimulated the proliferation of LPS-treated allogeneic B cells, and augmented the secretion of IgG by LPS-treated autologous B cells. Final cell yields were 6 x 10(5) to 8 x 10(5) cells per chicken with >95% purity. In summary, this combination of methods using Abs against E. tenella and CD45 made it possible for the first time to obtain a highly enriched IDCs and FDCs which are functionally active in chickens. This novel method will enable the detailed biochemical and immunological characterizations of avian dendritic cells and facilitate the investigation of their role in initiating immune response in normal and disease states.
Assuntos
Galinhas , Coccidiose/veterinária , Células Dendríticas Foliculares/citologia , Células Dendríticas/citologia , Eimeria tenella/imunologia , Doenças das Aves Domésticas/parasitologia , Animais , Antígenos de Protozoários/imunologia , Ceco/imunologia , Ceco/parasitologia , Coccidiose/imunologia , Coccidiose/parasitologia , Células Dendríticas/imunologia , Células Dendríticas/ultraestrutura , Células Dendríticas Foliculares/imunologia , Células Dendríticas Foliculares/ultraestrutura , Immunoblotting/veterinária , Imunoglobulina G/imunologia , Imuno-Histoquímica/veterinária , Interferon gama/imunologia , Antígenos Comuns de Leucócito/imunologia , Tecido Linfoide/imunologia , Tecido Linfoide/parasitologia , Microscopia Eletrônica de Transmissão/veterinária , Microscopia de Fluorescência/veterinária , Doenças das Aves Domésticas/imunologiaRESUMO
The purpose of this study was to characterize the ultrastructure of lymphoid tissue from HIV/AIDS patients and to evaluate it as a reservoir and source of HIV. HIV has been demonstrated in lymph nodes and tonsils and adenoids, by immunohistochemistry (IHC), in situ hybridization (ISH), and transmission electron microscopy (TEM), to be associated with germinal center (GC) follicular dendritic cells (FDC). The presence of HIV in the larger gastrointestinal tract-associated lymphoid tissue (GALT) has been much less studied. Whether FDC themselves are productively infected by HIV in any of the lymphoid sites is controversial. Lymph nodes, tonsils, and gastrointestinal biopsies were fixed in neutral buffered glutaraldehyde and prepared for TEM. Mature HIV particles were abundant in GC of hyperplastic lymph nodes, tonsils, and the GALT. They were enmeshed within an electron-dense matrix associated with an all-encompassing branching FDC network of processes. HIV particles were seen budding from both FDC and lymphocytes. The greatest numbers of particles were seen in hyperplastic lymphoid tissue from untreated individuals and in lymph nodes co-infected with opportunistic organisms, such as Mycobacterium avium complex. In addition to HIV, unidentifiable "particles" of varying sizes, possibly including other viruses, were regularly seen in association with FDC. Ultrastructural study graphically demonstrated the abundance of HIV particles associated with the complex FDC network of hyperplastic lymph nodes, tonsils, and GALT. HIV was shown to productively infect FDC, as well as lymphocytes.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , HIV/isolamento & purificação , Tecido Linfoide/ultraestrutura , Síndrome da Imunodeficiência Adquirida/virologia , Biomarcadores/análise , Biópsia , Células Dendríticas Foliculares/química , Células Dendríticas Foliculares/ultraestrutura , Células Dendríticas Foliculares/virologia , Trato Gastrointestinal/ultraestrutura , Trato Gastrointestinal/virologia , HIV/fisiologia , HIV/ultraestrutura , Humanos , Hiperplasia , Imuno-Histoquímica , Linfonodos/ultraestrutura , Linfonodos/virologia , Tecido Linfoide/virologia , Microscopia Eletrônica de Transmissão , Tonsila Palatina/ultraestrutura , Tonsila Palatina/virologia , Receptores de Complemento 3d/análise , Replicação ViralRESUMO
In this study, co-localization between sympathetic neural fibres and the follicular dendritic cells (FDCs) network was observed within the mouse spleen by confocal technology. Immunohistochemical techniques were used to reveal the rare interactions between the FDCs network and sympathetic neural fibres. We estimated the frequency of three kinds of close interactions which could be defined as overlaps, contacts or neural fibres closer than 10 microm from a FDCs network. Using these estimates, a comparison was made between five uninfected mouse strains exhibiting the same Prnpa genotype but showing different incubation periods when inoculated with primary bovine spongiform encephalopathy (BSE)-infected brain. In prion disease, infectivity is generally detected in the spleen much earlier than in the brain, especially after peripheral inoculation. The way by which the infectious agent reaches the central nervous system is still unclear. From the five mouse strains, we obtained differences in the proportion of splenic FDCs networks with close interactions. Our work suggests that the percentage of splenic FDCs networks with at least one sympathetic neural fibre in close vicinity may influence the length of incubation period.
Assuntos
Fibras Adrenérgicas/ultraestrutura , Células Dendríticas Foliculares/ultraestrutura , Baço/inervação , Baço/ultraestrutura , Sistema Nervoso Simpático/ultraestrutura , Animais , Bovinos , Comunicação Celular , Encefalopatia Espongiforme Bovina/genética , Encefalopatia Espongiforme Bovina/imunologia , Encefalopatia Espongiforme Bovina/transmissão , Feminino , Imunofluorescência , Predisposição Genética para Doença , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Proteínas Priônicas , Príons/genética , Especificidade da Espécie , Baço/imunologiaRESUMO
Follicular dendritic cells (FDCs) are immune accessory cells found in the follicles of secondary lymphoid organs where they promote B cell maturation in germinal centers (GCs) that develop following antigen exposure. Recently, we published a method for isolating functional murine FDCs in high purity. We reasoned that disruption of FDC reticula in vivo would alter FDC morphology. The present study was undertaken to determine the morphological features of isolated FDCs. FDC-M1 and immune complex (IC) labeling were used to identify FDCs in isolated preparations. Results at the light-microscopic level revealed that isolated FDCs trapped ICs, expressed FDC-M1 and cadherins, but generally appeared non-dendritic. However, at the ultrastructural level, the majority of FDCs exhibited dendrites and typical euchromatic nuclei that appeared as single, bilobed, or double nuclei. Based on morphology, four varieties of FDCs were distinguishable, possibly indicative of differences in maturity. Remarkably, ICs trapped by FDCs showed a distinctive periodic arrangement consistent with that known to induce immune responses by thymus independent-2 (TI-2) antigens that engage and cross-link multiple B cell receptors. The ability of FDCs to trap ICs and then display these T-cell-dependent antigens with repeating periodicity suggests that multiple B cell receptors are cross-linked by antigen on FDCs, thus promoting B cell stimulation and proliferation. Rapid proliferation is characteristic of the GC reaction, and the arrangement of T-dependent antigens in this periodic fashion may help to explain the profuse B cell proliferation in the GC microenvironment.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/ultraestrutura , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Superfície/imunologia , Caderinas/metabolismo , Núcleo Celular/ultraestrutura , Separação Celular/métodos , Extensões da Superfície Celular/ultraestrutura , Estruturas Citoplasmáticas/ultraestrutura , Dendritos/ultraestrutura , Células Dendríticas Foliculares/citologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Microscopia Eletrônica , Ligação Proteica , Coloração e RotulagemRESUMO
Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor arising most frequently in lymph nodes with only few reports of extranodal locations. We report the case of a 35-year-old man with a large retroperitoneal mass. Histologically the tumor was composed of highly pleomorphic cells exhibiting some uncommon features such as an epithelioid appearance, cystic spaces, and multinucleated cells with morphologic features of emperipolesis. Immunohistochemically the neoplastic cells were immunoreactive for CD21, CD23 and CD35. A previously unreported expression of neuroendocrine markers (Synaptophisyn and Neuron-Specific-Enolase) was present. Ultrastructurally no neuroendocrine secretory granules were detected. FDCS can mimic a wide variety of other malignant tumors, and a correct diagnosis requires exclusion of other neoplasms and immunohistochemical confirmation.
Assuntos
Neoplasias Abdominais/diagnóstico , Biomarcadores Tumorais/análise , Células Dendríticas Foliculares , Sarcoma/diagnóstico , Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/ultraestrutura , Adulto , Células Dendríticas Foliculares/ultraestrutura , Humanos , Imuno-Histoquímica , Masculino , Radiografia , Receptores de Complemento 3b/análise , Receptores de Complemento 3d/análise , Receptores de IgE/análise , Sarcoma/diagnóstico por imagem , Sarcoma/ultraestruturaRESUMO
Follicular dendritic cells (FDCs) reside in germinal centers in which their dendrites interdigitate and form non-mobile networks. FDC purification requires the use of collagenase and selection columns and leaves FDCs without detectable dendrites when examined by light microscopy. We have reasoned that isolated FDCs might reattach to a collagen matrix, extend their processes, and form immobile networks in vitro. As a test for this, cells were plated on collagen type I, laminin, biglycan, and hyaluronan. After 12 h, 80%-90% of FDCs adhered to all tested matrices but not to plastic. Within 2 weeks, FDCs adhering to type I collagen had spread out and had begun to acquire processes with occasional interconnections. By day 30, most FDCs had fine processes that formed networks through interdigitation with neighboring cells. FDC identity was confirmed by FDC-M1 labeling, immune complex trapping, and retention by FDCs in the networks. Scanning electron microscopy confirmed that groups of FDCs were in networks composed of convolutions and branching dendrites emanating from FDC cell bodies. In vivo, collagen type I was co-localized with FDCs, 5 h after challenge of immune mice with antigen. However, 2 days later, the collagen type I fibers were largely found at the periphery of the active follicles. Flow cytometry established the expression of CD29 and CD44 on FDCs; this may have partly mediated FDC-collagen interactions. Thus, we report, for the first time, that FDCs attach to collagen type I in vitro and regenerate their processes and networks with features in common with networks present in vivo.
Assuntos
Comunicação Celular/fisiologia , Extensões da Superfície Celular/metabolismo , Colágeno Tipo I , Células Dendríticas Foliculares/metabolismo , Receptores de Hialuronatos/biossíntese , Integrina beta1/biossíntese , Animais , Extensões da Superfície Celular/imunologia , Extensões da Superfície Celular/ultraestrutura , Células Cultivadas , Colágeno Tipo I/imunologia , Células Dendríticas Foliculares/imunologia , Células Dendríticas Foliculares/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Fatores de TempoRESUMO
Biochemical, genetic, and immunological studies of follicular dendritic cells (FDCs) have been hampered by difficulty in obtaining adequate numbers of purified cells in a functional state. To address this obstacle, we enriched FDCs by irradiating mice to destroy most lymphocytes, excised the lymph nodes, and gently digested the nodes with an enzyme cocktail to form single cell suspensions. The FDCs in suspension were selected using the specific mAb FDC-M1 with magnetic cell separation technology. We were able to get nearly a million viable lymph node FDCs per mouse at about 90% purity. When examined under light and transmission electron microscopy, the cytological features were characteristic of FDCs. Furthermore, the cells were able to trap and retain immune complexes and were positive for important phenotypic markers including FDC-M1, CD21/35, CD32, CD40, and CD54. Moreover, the purified FDCs exhibited classical FDC accessory activities including: the ability to co-stimulate B cell proliferation, augment antibody responses induced by mitogens or antigens, maintain B cell viability for weeks, and protect B lymphocytes from anti-FAS induced apoptosis. In short, this combination of methods made it possible to obtain a substantial number of highly enriched functional murine FDCs.
Assuntos
Células Dendríticas Foliculares/imunologia , Separação Imunomagnética/métodos , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/análise , Antígenos de Superfície/imunologia , Apoptose/imunologia , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Contagem de Células , Núcleo Celular/ultraestrutura , Proliferação de Células , Extensões da Superfície Celular/ultraestrutura , Sobrevivência Celular , Técnicas de Cocultura , Células Dendríticas Foliculares/citologia , Células Dendríticas Foliculares/ultraestrutura , Imunoglobulina G/imunologia , Molécula 1 de Adesão Intercelular/análise , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Ovalbumina/imunologia , Molécula 1 de Adesão de Célula Vascular/análiseRESUMO
Dendritic cells are antigen-presenting cellsfound in almost every type of tissue, includinglymphatic tissue, blood and skin. In the intestinaltract, these cells are likely to play a pivotalrole in the initiation and regulation of immuneresponses. Our earlier study of the human colonand ileum revealed the presence of zinc iodideosmium-positive dendritic cells. In the presentstudy we demonstrate the presence of ZIO-positivedendritic cells in the human appendix.ZIO-positive cells were seen in the region ofcrypts of Lieberkühn as well as in the surfaceepithelium. The cells showed a single longprocess directed towards the lumen. They werelong, slender, and triangular. In the region ofthe lymphoid follicle, two different types ofdendritic cells were noted. The follicular dendriticcells present in the germinal center werefew in number, larger in size and with thickdendritic processes. However, in the mantlezone typical dendritic cells were seen. Theywere smaller in size and had many thin processes.The distribution of dendritic cells in thehuman appendix confirms the role of theappendix in the immune response (AU)
No disponible
Assuntos
Feminino , Adulto , Humanos , Osmio/análise , Zinco/análise , Iodetos/análise , Células Dendríticas Foliculares/ultraestrutura , Apêndice/ultraestrutura , ColectomiaRESUMO
Follicular dendritic cell tumor (FDCT) is a rare tumor mainly located in laterocervical lymph nodes. We report one case of mediastinal FDCT associated with a history of bullous skin disease and clinically obvious immunosuppression. This tumor was characterized by heavy mast cell infiltration. Mast cells were in close relationship with tumor cells as demonstrated by ultrastructural examination and their presence are probably related with the strong expression of mast cell chemoattractants as fraktalkine and stromal cell-derived factor-1alpha by tumor cells. The long follow-up period of more than 17 years allowed to us assess the relatively indolent evolution of this tumor characterized by three slowly growing local recurrences without metastasis.
Assuntos
Células Dendríticas Foliculares/patologia , Linfoma Folicular/patologia , Neoplasias do Mediastino/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Quimiocina CXCL12 , Quimiocinas CXC/análise , Fatores Quimiotáticos/análise , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/ultraestrutura , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Masculino , Mastócitos/química , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/metabolismo , Microscopia Eletrônica , Pessoa de Meia-Idade , RNA Viral/genética , Vimentina/análiseRESUMO
The pathogenesis of hyaline vascular Castleman disease (HVCD) is poorly understood. Although generally considered reactive in nature, a subset of cases has been shown to harbor focal proliferations of stromal cells, such as follicular dendritic cell (FDC) and angiomyoid proliferations. We report two typical cases of HVCD with cytogenetic anomalies: one was t(1;22)(qter;q13) and the other was t(7;8)(q37.3;q12) in cultured stromal cells, as demonstrated by conventional cytogenetic analysis. The cultured cells were immunoreactive for smooth muscle actin but negative for CD21, CD31, and CD34, and ultrastructurally possessed thin filaments (5-7.5 nm) with dense bodies, and pinocytotic vesicles, characteristic of smooth muscle cells. The lack of monoclonality of lymphoid cells in lesional tissues by immunohistochemical and molecular analyses also supports the origin of these anomalies from the stromal cells, most likely myoid cells. Moreover, the absence of overt stromal proliferations suggests that cytogenetic changes in stromal cells of HVCD precede histologic evidence of stromal overgrowth, which may account for the occurrence of angiomyoid proliferations arising in some cases of HVCD. Further studies with more cases are needed to decipher whether part or even most of HVCD cases bear genetic changes in the beginning of the disease without morphologically stromal overgrowth.
Assuntos
Hiperplasia do Linfonodo Gigante/genética , Hiperplasia do Linfonodo Gigante/patologia , Aberrações Cromossômicas , Células Dendríticas Foliculares/patologia , Adulto , Antígenos CD34/metabolismo , Hiperplasia do Linfonodo Gigante/diagnóstico , Células Cultivadas , Criança , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/ultraestrutura , Feminino , Humanos , Hialina/metabolismo , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores de Complemento 3b/metabolismo , Receptores de Complemento 3d/metabolismo , Células Estromais/patologiaRESUMO
Conjunctiva-associated lymphoid tissue (CALT) is a part of the eye-associated lymphoid tissue (EALT) at the ocular surface. Its lymphoid follicles are usually characterized by using light microscopy, but its ultrastructure remains largely unknown. In this study, flat whole-mount conjunctival tissues (n = 42) from 21 young adult rabbits were investigated native in reflected light, and further stained and cleared (n = 6), in paraffin histology sections (n = 6), scanning electron microscopy (SEM, n = 4) and transmission electron microscopy (TEM, n = 4). Secondary lymphoid follicles accumulated into a dense group nasally towards the lacrimal punctum of the lower lid. High endothelial venules (HEV) with typical ultrastructure occurred in the parafollicular zone. The bright germinal centre (GC) contained lymphoblasts, follicular dendritic cells, apoptotic cells and tingible body macrophages. The follicle-associated epithelium (FAE) was devoid of goblet cells and contained groups of lymphoid cells. TEM showed these cells to be located in cytoplasmic pockets of superficial electron-lucent cells with a thin cytoplasmic luminal lining that contained a fine filament meshwork and numerous endocytotic vesicles. These M-cells were sitting between and on top of the ordinary dense epithelial cells that were located basally and formed pillar-like structures. In stereoscopic SEM, the surface cells were very large, had a polygonal outline and covered cavernous spaces. The rabbit has a CALT with typical follicular morphology, including HEV for regulated lymphocyte migration and epithelial cells with ultrastructural characteristics of M-cells that allow antigen transport as indicated by the GC-reaction. The arrangement of these M-cells on top of and between epithelial pillar cells may reflect a special structural requirement of the multilayered CALT FAE.
Assuntos
Túnica Conjuntiva/imunologia , Tecido Linfoide/ultraestrutura , Coelhos/imunologia , Animais , Apoptose , Células Dendríticas Foliculares/ultraestrutura , Células Endoteliais/ultraestrutura , Células Epiteliais/ultraestrutura , Centro Germinativo/ultraestrutura , Imunidade nas Mucosas , Vasos Linfáticos/ultraestrutura , Linfócitos/ultraestrutura , Tecido Linfoide/imunologia , Macrófagos/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fixação de TecidosRESUMO
Follicular dendritic cell sarcoma is a tumor of recent description and characterization; it is often underdiagnosed because it is easily confused with other entities. Three cases of follicular dendritic cell sarcoma are described in the present article. The first occurred in the parapharyngeal space in a 29-year-old woman who developed multiple recurrences over the span of 10 years. The second was located in the left tonsil in a 48-year-old man, and the third case developed in the parapharyngeal space in a 26-year-old man. All cases were positive for CD21 and CD35 and ultrastructurally they displayed a morphologic spectrum. The first case featured spindle cells with interdigitated long cell processes joined by well-developed desmosomes. In the other two cases there were round to ovoid cells with interwoven processes connected by occasional desmosomes. Including these three cases, a total of 20 follicular dendritic cell sarcoma of the pharyngeal region have been reported to date. The clinical behavior of these tumors is similar to other low-grade sarcomas.
Assuntos
Células Dendríticas Foliculares/patologia , Neoplasias Faríngeas/patologia , Sarcoma/patologia , Adulto , Biomarcadores Tumorais/análise , Células Dendríticas Foliculares/química , Células Dendríticas Foliculares/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/química , Neoplasias Faríngeas/ultraestrutura , Receptores de Complemento 3b/análise , Receptores de Complemento 3d/análise , Sarcoma/química , Sarcoma/ultraestrutura , Tomografia Computadorizada por Raios XRESUMO
We describe two elderly patients with follicular lymphoma (FL) involving the skin and superficial soft tissues, with a striking proliferation of follicular dendritic cells (FDC). In addition, one patient had bone marrow involvement by FL. Histopathologically, the most remarkable feature in both cases seen at low magnification was a striking pallor of the constituent cells, which were arranged in fascicles, whorls, and round islands. The majority of the cells had the typical cytologic features of FDCs. They were intimately intermingled with centroblasts and centrocytes. A large amount of the clear cytoplasm and the pale nuclei of FDCs, which predominated in the tumors, caused the striking overall pallor of the lesions. Small reactive lymphocytes were scattered between the fascicles. A vague follicular growth pattern was seen only focally. The mantle zones were markedly reduced or absent so that the follicles were seen lying unseparated. The close intermixture of the FDCs and the germinal center cells was responsible for the FDCs appearing to be decorated with B-associated marker, and the germinal center cells seemed to be stained to some degree with FDC-markers. The tumor bulk demonstrated a diffuse and strong reaction with CD10, CD20, CD21, CD35, and stained weakly with CD79a. Fascin and CD23 showed only a weak and focal staining pattern. Bcl-2 decorated large centroblasts and small reactive T-cells. The tumor bulk was negative for actin, EMA, cytokeratins, vimentin, desmin, and factor XIIIa. The proliferative index was rather low; MIB-1 mainly decorated large centroblasts. No monoclonal rearrangement of IgH genes was detected. Epstein-Barr virus was not identified. Electron microscopy revealed typical features of FDCs intermingled with germinal center cells. Such cases may represent a diagnostic pitfall, as FDC overgrowth can mask FL and give the neoplasm the appearance of FDC sarcoma/tumor. We believe that, in both cases, the FDC proliferation had a reactive character.