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At least 19 recordsLinked to original sources

PubMed1983

Monoclonal antibody Ki-M4 specifically recognizes human dendritic reticulum cells (follicular dendritic cells) and their possible precursor in blood.

Ki-M4, a new IgG3 monoclonal antibody, selectively recognizes dendritic reticulum cells (DRC; follicular dendritic cells) in all human lymphatic organs, as tested by the immunoperoxidase method on the light and electron microscopic level. This antibody was raised against separated lysosomes of the 12-0-tetradecanoyl phorbol-13-acetate (TPA) stimulated permanent cell line, U-937, derived from a human histiocytic lymphoma. No cross-reactivity was encountered in epithelial and mesenchymal cells, including macrophages and other cells detectable in bronchial and peritoneal lavages. In the nonadherent fraction of the mononuclear blood cells collected from the interphase of a Ficoll-Urografin gradient (density = 1.077 g/ml), 0.1 per million of the cells hitherto not classified as monocytes or lymphocytes showed a strong reaction. All other separated blood cell types were devoid of any reactivity. The observation that DRC share a highly restricted, and thus specific, antigen with a small but distinct subpopulation of mononuclear leukocytes implies their blood derivation.

Antibodies, Monoclonal↗

PubMed2004

FDC-B1: a new monoclonal antibody directed against bovine follicular dendritic cells.

Follicular dendritic cells (FDCs) are a unique population of accessory cells located in the light zone of the germinal centres of lymphoid follicles. Their involvement in the generation of humoral immune responses implies a potential role for these cells in many disorders. Indeed, in prion diseases, FDCs seem to be the major sites of extraneuronal cellular prion protein expression and the principal sites of the infectious agent accumulation in lymphoid organs. The identification of FDC is useful for the analysis of their distribution in reactive lymphoid tissue as well as in pathological conditions. The production and characterisation of a new mouse monoclonal antibody directed against bovine follicular dendritic cells (FDC-B1) is reported. The antigen detected by FDC-B1 is expressed exclusively on the surface of FDCs in ruminant lymphoid organs. The antigen has an approximate molecular weight of 28 kDa.

Animals↗

PubMed1994

Moabs MAS516 and 5B5, two fibroblast markers, recognize human follicular dendritic cells.

Follicular dendritic cells (FDC) are only located within follicles of secondary lymphoid tissues. The origin of this peculiar cell type is not clearly defined. To contribute to this study, we applied two monoclonal antibodies (MAS516 and 5B5) considered as specific for fibroblasts to tonsil cryosections and to isolated follicular dendritic cells. On the basis of an enzyme cocktail digestion of human tonsils and a fractionation procedure on albumin gradients, FDC can be prepared in the form of cell aggregates with associated lymphoid cells. MAS516 reacts with surface membrane molecules expressed by human fibroblasts, tissue macrophages and peripheral blood monocytes. With immunoperoxidase assays on tonsil cryosections connective tissue cells and macrophages are stained. Inside germinal centres, heavy labelling of the light zone was found. The MAS516 staining pattern is very similar to that of specific FDC markers DRC-1 or BU10. All isolated FDC reacted with MAS516 antibody. 5B5, considered as a typical fibroblast marker, reacts with human prolyl-4-hydroxylase which is an intracellular enzyme related to collagen biosynthesis. In cryosections, interfollicular and capsular areas showed 5B5 positive connective tissue fibroblasts. In germinal centres, some cells presenting features of FDC were 5B5 positive. After cell separation, 25%-50% of the isolated FDC were labelled with this antibody. This positivity of some FDC for 5B5 antibody may support the idea of their fibroblastic origin. The combination of observations realized in situ and after cell purification ensured an unequivocal recognition and identification of FDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1985

The function and origin of follicular dendritic cells.

Follicular dendritic cells (dendritic reticular cells) in germinal centres bind antigen-antibody complexes via C3 receptors and retain the complexes at their surface for long periods of time. The follicular dendritic cells (FDC) are distinct from macrophages and from dendritic cells found in T-dependent areas, and are not derived from bone marrow stem cells. On histological evidence it has been proposed that they are derived from reticulum cells. Complexes are probably transported to FDC by a subpopulation of B cells in the marginal zone. Binding of complexes to FDC causes germinal centre enlargement and is a very efficient, and possibly essential stimulus to the generation of B memory cells which recognize epitopes on antigen or antibody in the complexes. An hypothesis is discussed which draws together these observations and suggests that antigen on FDC plays a central role in control of humoral immunity.

Animals↗

PubMed2006

Taking control of follicular dendritic cells.

Follicular dendritic cells signal the formation of B cell follicles as well as B cell activation, proliferation, and maturation. However, the precise molecular pathways controlling these processes are just beginning to be unraveled.

Animals↗

PubMed2003

Expression of CD137 (4-1BB) on human follicular dendritic cells.

Follicular dendritic cells (FDCs) are the antigen (Ag)-trapping accessory cells of the germinal centres (GCs), essential for the development of humoral immune responses and memory. FDCs reside in the microenvironment of secondary lymphoid tissue where Ag-activated B cells expand, and undergo isotype switching and affinity maturation prior to becoming memory B cells. In addition to delivering Ag, FDCs also provide potent nonspecific accessory signals to the B cells, which are important for the GC reaction. In this report, we show that human tonsilar FDCs express the costimulatory molecule CD137. Surface expression of CD137 on FDCs was confirmed by immunofluorescent labelling and fluorescence-activated cell sorter analysis. CD137 was also highly expressed by the human cell line HK, which displays many characteristics of in vivo FDCs. The interaction between B cells and FDCs is essential for the GC reactions, and our finding suggests that CD137 plays a role in FDC-regulated B-cell responses.

Antigens, CD↗

PubMed1985

5-Nucleotidase activity in isolated follicular dendritic cells.

Follicular dendritic cells isolated from mouse lymph nodes were incubated in the presence of AMP to test 5-nucleotidase (5-Nase) activity. Ultrastructural observations showed the presence of 5-Nase on external membranes but also some activity inside the nucleus. 5-Nase was found associated to Fc receptors labelled with homologous immunoglobulins fixed on colloidal gold particles. Lymphocytes and macrophages, found in association with the follicular dendritic cells, were either 5-Nase positive or negative. The hypothetical roles played by 5-Nase in germinal centers are discussed.

5'-Nucleotidase↗

PubMed2001

Persistence of infectious HIV on follicular dendritic cells.

Follicular dendritic cells (FDCs) trap Ags and retain them in their native state for many months. Shortly after infection, HIV particles are trapped on FDCs and can be observed until the follicular network is destroyed. We sought to determine whether FDCs could maintain trapped virus in an infectious state for long periods of time. Because virus replication would replenish the HIV reservoir and thus falsely prolong recovery of infectious virus, we used a nonpermissive murine model to examine maintenance of HIV infectivity in vivo. We also examined human FDCs in vitro to determine whether they could maintain HIV infectivity. FDC-trapped virus remained infectious in vivo at all time points examined over a 9-mo period. Remarkably, as few as 100 FDCs were sufficient to transmit infection throughout the 9-mo period. Human FDCs maintained HIV infectivity for at least 25 days in vitro, whereas virus without FDCs lost infectivity after only a few days. These data indicate that HIV retained on FDCs can be long lived even in the absence of viral replication and suggest that FDCs stabilize and protect HIV, thus providing a long-term reservoir of infectious virus. These trapped stores of HIV may be replenished with replicating virus that persists even under highly active antiretroviral therapy and would likely be capable of causing infection on cessation of drug therapy.

Animals↗

PubMed1997

Expression of cytokine receptors on follicular dendritic cells.

Follicular dendritic cells (FDCs) in the lymphoid follicle (LF) are essential to the sequential processes of B-cell proliferation, selection, and differentiation. Although the importance of some cytokines in these processes has been pointed out, there is little information about the follicular localization of their receptors. We investigated, with special reference to FDCs, the localization of cytokine receptors as well as cytokines themselves in human tonsils by several means, including immunochemistry, immunoelectron microscopy, reverse transcriptase polymerase chain reaction, and in situ hybridization. FDCs in the follicular apical light zone expressed transforming growth factor-beta receptor II (TGF-betaR II), granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRalpha; CDw116), tumor necrosis factor receptor I (TNFR I; CD120a), interleukin-1 receptor II (IL-1R II; CDw121b), IL-2 receptor beta (IL-2Rbeta; CD122), IL-4 receptor (IL-4R; CDw124), and IL-6 receptor (IL-6R; CD126), among the 10 receptors examined. Those in the basal light zone expressed strongly TNFR I and weakly GM-CSFR alpha, IL-1R II, IL-2Rbeta, IL-4R, and IL-6R, and often those in the outer and mantle zones expressed GM-CSFR alpha, IL-4R, and IL-6R. FDCs in the apical light zone expressed only TGF-beta among the 7 cytokines examined. On the other hand, follicular lymphocytes mainly in the light zone expressed 9 kinds of receptors, with the exception being TGF-betaR II; expression was rather frequent for TNF-alpha, IL-1alpha, and IL-2 and less frequent for TGF-beta, GM-CSF, IL-4, and IL-6. These data indicate that only FDCs mainly in the light zone express many cytokine receptors, although FDCs may produce the cytokine, TGF-beta. Cytokines may act not only on some follicular lymphocytes but also on most FDCs in the light zone expressing cytokine receptors.

Animals↗

PubMed2006

TC1(C8orf4) is upregulated by IL-1beta/TNF-alpha and enhances proliferation of human follicular dendritic cells.

Follicular dendritic cells (FDC) play crucial roles in immune regulation. TNF-alpha has been shown to be essential to the FDC network. However, the molecular regulation of FDC proliferation has not been characterized. Here, we show that TC1(C8orf4), a novel positive regulator of the Wnt/beta-catenin pathway in vertebrates, is upregulated by IL-1beta and TNF-alpha in the human FDC-like line HK. TC1 enhances HK cell proliferation, while TC1-knockdown inhibits the proliferation induced by IL-1beta, suggesting a role of TC1 as a regulator of FDC proliferation. The regulation by pro-inflammatory cytokines suggests that TC1 might be implicated in linking local inflammation to immune response by stimulating FDC.

Base Sequence↗

PubMed1985

Retention of immune complexes by Fc receptors on mouse follicular dendritic cells.

Follicular dendritic cells (FDC) are located inside lymph follicles and are mainly characterized by their capacity to retain antigens. We investigated this aspect in mice lymph nodes by using bovine serum albumin (BSA) labelled with 5-nm colloidal gold particles and homologous anti-BSA antibodies bound to 20-nm gold particles. Gold-labelled BSA injected alone in non-immunized mice was only rarely found in FDC cytoplasmic interdigitations. Injected in the form of immune complexes, it was retained by FDC. Antigen-free anti-BSA antibodies injected under similar conditions as immune complexes were always found in draining lymph nodes in the same locations as BSA-anti-BSA immune complexes. F(ab')2 from mouse immunoglobulins linked to colloidal gold particles were very rarely found between the FDC extensions, whereas it was intensely phagocytosed by macrophages. Our study permitted precise ultrastructural localization between FDC cytoplasmic extensions or inside macrophages and other cells of the lymph nodes, but it also pointed out that homologous antibodies linked to colloidal gold particles might be retained by FDC in the absence of antigens. These observations, carried out with colloidal gold, were checked by using 125I-labelled anti-BSA antibodies. Complement activation determinations of gold-labelled antibodies or immune complexes showed that antibodies or immune complexes fixed on colloidal gold particles do not activate the complement. This observation enabled us to conclude that Fc receptors play a significant part in the retention of gold-labelled antibodies or immune complexes by FDC of lymph nodes.

Animals↗

PubMed1989

Isolation and antigenic profile of follicular dendritic cells.

Follicular dendritic cells (FDC) were isolated from human tonsils and adenoids. With a simple modification of an isolation method described previously, FDC could be enriched up to 50%. The isolated FDC were characterized immunocytochemically. In contrast to previous studies, CD4 antigen was not detected on freed FDC, thereby suggesting that the CD4 molecule does not play a role in the infection process of FDC in AIDS, as has been demonstrated for T helper cells. Fc receptors could not be found on FDC by the panel of monoclonal antibodies applied, whereas C3 receptors were observed in abundance. Therefore, antigen trapping in germinal centres most probably involves only C3 receptors. This concept is in contrast with the current one (also developed on isolated cells), which postulates the involvement of Fc receptors. The extent to which C3 receptors are involved in the pathogenesis of AIDS will be examined in further studies.

Adenoids↗

PubMed1984

Functional study of human tonsillar follicular dendritic cells.

Follicular dendritic cells (FDC) isolated from human tonsils and adenoids appear as round clusters where the FDC surround lymphoid cells. Using fluorescein and colloidal gold labelled antibodies we determined their surface antigens, the immunoglobulins they fix and the cells they envelope. Isolated FDC react with specific anti-FDC antibodies but also with an anti-monocyte/macrophage antibody and with anti-HLA-DR antibodies. They retain IgG, IgM, IgA and IgE but not IgD immunoglobulins; this retention occurs, according to our results, via their Fc and C3b receptors. The cells they envelope are mainly B cells, but also occasionally T helper cells. T suppressor cells were only rarely found in contact with FDC. We suggest that FDC create a micro-environment favourable to the proliferation and differentiation of B cells during the humoral response.

Adenoids↗

PubMed1998

Expression of MUC-1 glycoprotein in plasma cells, follicular dendritic cells, myofibroblasts and perineurial cells: immunohistochemical analysis using three monoclonal antibodies.

Normal and malignant plasma cells (PC), follicular dendritic cells (FDC), myofibroblasts (MFB) and perineurial cells (PNC) were investigated for the expression of MUC-1 glycoprotein (MUC-1gp) by immunohistochemical and immunoelectron microscopic techniques using monoclonal antibodies E29, 115D8, DF3 and a combination of the three. MUC-1 glycoprotein-positive PC detected by the combined antibodies were frequently seen in a variety of pathological lesions tested, including chronic cervicitis, chronic synovitis, Hodgkin's disease, allergic rhinitis and sinusitis, tuberculous lymphadenitis, foreign body granuloma, multiple myeloma, and chronic tonsillitis. In the lesions containing MUC-1gp-positive PC, the infiltration of immunoglobulin (Ig) E PC and/or IgE-bound mast cells was significantly increased, but MUC-1gp-positive PC did not contain any specific immunoglobulin heavy or light chains. The findings suggest that the expression of MUC-1 gp in PC, although not restricted to IgE-class cells, may be induced in an allergic status. Plasma cells and PNC mainly reacted with the antibodies E29 and 115D8, while FDC and MFB were principally reactive with the antibody DF3. In some cases of multiple myeloma, the neoplastic PC were predominantly immunoreactive with DF3. The results indicate: (i) the epitopic variability of MUC-1gp molecules expressed on the non-epithelial cells; and (ii) the epitopic alterations during malignant transformation. It should also be noted that the expression of MUC-1gp in the non-epithelial cells represents a pitfall in histopathological diagnosis.

Antibodies, Monoclonal↗

PubMed1995

Expression of vascular cell adhesion molecule-1 by follicular dendritic cells.

Follicular dendritic cells are the major supporting cell of the germinal center microenvironment. The major function of follicular dendritic cells is to present antigen to B cells in secondary lymphoid tissues. Through cell-cell interactions, FDCs are hypothesized to be central to the regulation of normal B cell growth and differentiation. The major receptor-ligand pair which mediates B cell-FDC adhesion is the beta 1 integrin VLA-4, present on B cells and VCAM-1 expressed on FDCs. Follicular non-Hodgkin's lymphomas similarly employ this mechanism to bind to neoplastic germinal centers. The VCAM-1 molecule can exist as a 6 or 7 immunoglobulin domain form. The major form of VCAM-1 on activated endothelium is the 7 domain form. In this report we have determined by polymerase chain reaction of purified FDCs that they express predominantly mRNA for 7 domain VCAM-1. It is likely that the two forms of VCAM-1 are associated with distinct functions, therefore the expression of 7 domain VCAM-1 may be important in normal and neoplastic B cell-FDC interactions.

Base Sequence↗

PubMed2004

Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses.

CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is predominantly expressed on lymphoid and myeloid cells. CD38 has a significant role in B-cell function as some anti-CD38 antibodies can deliver potent growth and differentiation signals, but the ligand that delivers this signal in mice is unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG) (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen. Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only fresh ex vivo CD11c+ CD11b- DCs had cell surface CD38L. Anti-CD38 antibody blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection. CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC) class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was administered in vivo with antigen, IgG2a responses were significantly reduced, suggesting that B and T cells expressing CD38 may modulate the isotype of antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded FDC networks when administered in vivo. In conclusion, this study has identified a novel ligand for CD38 which has a role in functional interactions between lymphocytes and DCs or FDCs.

ADP-ribosyl Cyclase↗

PubMed1995

The human germinal centre cells, follicular dendritic cells and germinal centre T cells produce B cell-stimulating cytokines.

Cytokine gene expression was investigated in the germinal centre constituents of follicular dendritic cells and germinal centre T cells and compared to the mRNA expression of nongerminal centre tonsillar cells. Cells were isolated from human tonsils by preenrichment with MACS and subsequent FACS sorting. Cytokine gene expression was investigated by intronspanning RT-PCR for IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-alpha, IFN-beta, IFN-gamma, and TNF-alpha. Frequency of cytokine-producing cells and the cytokine production pattern of single cells were determined by single cell PCR. Furthermore, cytokine protein expression was investigated by immunohistology. Using these methods, we found a strong production of IL-1 beta mRNA and protein in a small percentage of FDC. Germinal centre T cells showed production of IL-2, IL-4, IL-10, IFN-gamma, and TNF-alpha mRNA. The mRNAs of these cytokines could also be detected at the single cell level; as they were produced in a high percentage of germinal centre T cells, whereas immunohistological staining was negative, we conclude that a high percentage of germinal centre T lymphocytes produce IL-2, IL-4, IL-10, IFN-gamma, and TNF-alpha in low concentrations in contrast to T cells outside the germinal centre, in which strong cytokine production in few cells was shown earlier.

B-Lymphocytes↗

PubMed1987

Influence of immunoglobulin isotypes and lymphoid cell phenotype on the transfer of immune complexes to follicular dendritic cells.

Follicular dendritic cells (FDC) are located only inside lymph follicles and are characterized mainly by their capacity to retain high amounts of immune complexes by their Fc or C3b receptors. In this work, we examine the influence of immunoglobulin isotypes and the subset of lymphoid cells (B or T) upon the transfer of immune complexes from lymphocytes to FDC. FDC isolated from mice lymph nodes by enzymatic digestion are able to fix, through Fc receptors, gold-labeled immune complexes presented by lymphoid cells. As demonstrated by electron microscopy, this transfer requires the establishment of close contacts between both cell types. Using different cell selection techniques we show that B lymphoid cells take up immune complexes more efficiently than do T lymphoid cells and transfer a larger number of them to FDC. This transfer mechanism is dependent on the immunoglobulin isotype: immune complexes constituted of IgG2a, IgG2b, and IgG1 isotypes are better transferred to FDC than those constituted of IgG3 and IgM.

Animals↗