Follicular Dendritic Reticulum Cells Research Articles

Diffuse Lymph-Nodes Microangiopathy as Concurrent Cause of Immunodeficiency in Long-Term Insulin-Dependent Diabetic Patients

Immune abnormalities have been demonstrated in vitro models in genetic (type1) autoimmune (type 2) and metabolic (type 1 and type 2) Insulin-Dependent Diabetes Mellitus (IDDM). However, the precise reason for increased susceptibility to frequent and protracted infections in diabetic patients is still unclear, despite a multitude of in vitro studies which have focused on the metabolic and functional modifications of immune cells Diabetes microangiopathy, which is a peculiar alteration of the disease, has been extensively described in the retina, renal glomeruli, skin, skeletal muscles, peripheral nerves, and other organs but not in lymph nodes. We report our histological and immunohistochemical observations in lymph-nodes removed in multiple sites during autopsy from four patients with long-term IDDM, severe lymphocytpenia and several infectious diseases during their life. The peculiar microangiopathic modifications made by presence of hyaline substance thickening basal membrane of thin vessels and capillaries appear concurrent with lymphodepletion of B and T cells dependent areas of lymph-nodes and with jointed marked reduction of Follicular Dendritic Reticulum Cells (FDRC). Indeed microangiopathy further compromise the traffic and diapedesis of T and B lymphocytes may prevent the transformation of endothelial cells into FDRC with severe immune failure of lymphoid follicles. The histological and immunohistochemical data in this study could provide additional insights into the complex problem of the immunodeficiency in diabetic patients.

Electron Microscopic Studies of Spleen in Chicken (Gallus domesticus)

Electron microscopic studies on spleen of layer chicken were done in various age groups ranging from day-old to forty weeks. The spleen was encapsulated by a connective tissue capsule and the trabeculae were poorly developed in all the age groups studied. The major cellular population of the white pulp included lymphoblasts, lymphocytes of various sizes, follicular dendritic cells and reticulum cells. The splenic red pulp was composed of pulp cords consisted of erythrocytes, reticular cells and lymphocytes of various sizes, macrophages, granulocytes, plasma cells and mast cells. The arterioles that continued into the red pulp formed sheathed capillaries or ellipsoids.

Late recurrence of Castleman’s disease with mixed angiomyoid, histiocytic reticulum cell, follicular dendritic cell stroma-rich proliferations: a case report and review of the literature

Castleman disease, hyaline vascular variant (HV-CD) involving lymph nodes is characterized by abnormal follicles with increased vascularity, hypervascular interfollicular tissue, absence of sinuses, and follicles having the characteristic “onion skin-like” appearance. We present a rare case of HV-CD, stroma-rich variant, which recurred less than 5 years after initial surgical therapy. The recurrent lesion varied in appearance from classical morphology of HV-CD with a stromal proliferation of follicular dendritic, angiomyoid cells, and histiocytic reticulum cells. Less than fifty cases of stroma-rich Castleman disease have been reported in the literature. To the best of our knowledge, this is the first case showing a mixed proliferation of stromal elements with rims of compressed normal lymphoid tissue and recurrence after surgical excision.

Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

BackgroundB7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC).MethodsExpression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients.ResultsCD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients.ConclusionExpression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC.

Primary mediastinal lymph node malignancy with features suggestive of dendritic cell sarcoma

A 56-year-old man underwent preoperative chest computed tomography to further evaluate a well defined mass in the middle lobe with subcarinal lymph node swelling. There was no pathological diagnosis established by either bronchoscopic biopsy specimens or computed tomography-guided percutaneous needle biopsy. The middle lobe and mediastinal lymph nodes were excised, then postoperative radiotherapy (60 Gy) was administered to the mediastinum. Results of histological and immunohistochemical study showed that the lung mass consisted of completely necrotic tissue and that the subcarinal lymph node was involved by malignant cells suggestive of dendritic cell sarcoma. Primary dendritic cell sarcoma of the mediastinal lymph node is extremely rare. Dendritic cell sarcoma is a neoplasm of reticular dendritic origin and includes both follicular dendritic cell sarcoma and interdigitating reticulum (or dendritic) cell sarcoma. These rare neoplasms may pose difficulty in pathologic diagnosis and treatment. Although our patient died of hepatic rupture due to dendritic cell sarcoma or gastric cancer metastases one year after surgery, complete surgical resection with or without postoperative radiotherapy may be an acceptable therapeutic option for localized dendritic cell sarcoma.

Classic follicular dendritic reticulum cell tumor of the lymph node developing in a patient with a previous inflammatory pseudotumor–like proliferation

Inflammatory pseudotumor (IPT) and follicular dendritic reticulum cell tumor (FDRCT) are rare entities of the lymph node characterized by spindle-cell proliferation. We report a case of a 31-year-old woman, who was admitted for biopsy of a lymph node in the left submandibular area. The microscopic examination revealed a proliferation of spindle cells, partially replacing the normal lymph node architecture, suggestive of an IPT. The preserved peripheral portion showed follicular hyperplasia with Castleman-like appearance. Six years later she presented with a new enlargement in the same submandibular area. The nodule was removed, and a diagnosis of a classic FDRCT of the lymph node was made. The present case is remarkable, and clinicopathological data show that IPT-like proliferations could be in some case an early presentation of FDRCT.

Follicular dendritic reticulum cell tumor mimicking inflammatory pseudotumor of the spleen

In the course of a routine clinical check up of the 54 year old male a splenic well circumscribed tumor like mass of 12 cm in diameter was discovered. Splenectomy with removal of splenic hilar lymph nodes and liver wedge biopsy were performed. Four years later the patient is symptom free. In the removed spleen the tumor like lesion showed a pattern consistent with the diagnosis of inflammatory pseudotumor. However, besides lymphocytes, plasma cells, macrophages, eosinophils and myofibroblasts a high number of slightly polymorphic, frequently binucleated cells positive for CD21 and CD23 were seen. These cells which were scattered or formed smaller or larger groups and fascicles were considered to represent follicular dendritic reticulum cells (FDRCs) and the lesion a FDRC tumor. Flow cytometric DNA ploidy analysis showed a hyperdiploid cell population inside the tumor like lesion. Besides FDRC tumors of high and of intermediate malignancy the present case may represent a low grade type of moderate proliferation activity. The FDRCs of the lesion and a few smaller spindle cells were EBER positive indicative of the presence of EBV. No EBER positive cells were seen in the uninvolved spleen.

Cloning of a complementary DNA encoding the unique dendritic cell antigen Ki-M9.

Human sinus-lining cells (SLC) of the lymph node sinuses most probably represent accessory cells for the primary humoral immune response and have been shown to express a unique antigen recognized by the monoclonal antibody Ki-M9. To characterize this SLC-specific antigen further, a spleen cDNA library established in the expression vector lambda gt-11 was searched immunochemically for clones expressing the Ki-M9 antigen. Two recombinant phage clones revealed a cDNA with an open reading frame of 1666 bp encoding a 68-kDa protein. When fused with an expression vector that codes for the bacterial maltose-binding protein (MBP), the purified MBP-Ki-M9 fusion protein could be clearly detected by Western blot analysis. Furthermore, in situ hybridization with Ki-M9 cDNA as a probe confirmed the SLC-specific expression of the cloned cDNA. Additionally, Ki-M9 mRNA transcripts were detected in follicular dendritic reticulum cells of the secondary germinal centers, in a few cells of the perifollicular zone of the spleen, in some sinusoidal cells of liver, and in thymic reticular cells. A sequence database research revealed a strong homology to a murine cDNA. By applying non-radioactive in situ hybridization on mouse tissue, strong expression in SLC of the lymph node and metallophilic cells of the spleen in mouse tissue could be seen indicating that the Ki-M9 cDNA is highly conserved in the two species. Further computer analysis of the deduced amino acid sequence of the Ki-M9 antigen showed a large number of potential glycosylation sites and a PEST motive, which are characteristic for rapidly degraded membrane bound proteins and represent prerequisites for the function of this cell system in initiating the humoral immune response.

Colocalization of the viral interleukin-6 with latent nuclear antigen-1 of human herpesvirus-8 in endothelial spindle cells of Kaposi's sarcoma and lymphoid cells of multicentric Castleman's disease

Human herpesvirus-8 (HHV-8) also called Kaposi's sarcoma-associated herpesvirus infects spindle cells in Kaposi's sarcoma (KS) and lymphoid cells in multicentric Castleman's disease (MCD). In KS cells, HHV-8 is mainly latent with the expression of latent nuclear antigen-1 (LNA-1), whereas in MCD both lytic and latent antigens are produced by lymphoid cells. We show by immunohistochemical labeling that in KS viral interleukin-6 (vIL-6) is expressed in rare spindle cells, whereas in MCD, vIL-6 is detectable in lymphoid cells around lymphoid follicles but also within the follicular dendritic reticulum cell network. The staining of apoptotic bodies with anti IL-6 antibody suggests the achievement of a complete lytic cycle in a subset of lymphoid cells. Interestingly, in MCD, some areas contained vascular spindle cells latently infected by HHV-8 on the basis of LNA-1 expression. This finding might imply that in MCD, both vascular and lymphoid cells proliferate in response to the viral infection. Double immunostaining with anti LNA-1 and anti vIL-6 in MCD and KS identifies 2 subsets of HHV-8 infected (vascular and lymphoid) cells, some with exclusive expression of LNA-1 and some with coexpression of vIL-6 and LNA-1. This suggests that in vivo the regulation of the expression vIL-6 and LNA-1 protein varies with the cell type. In addition, the detection of infected endothelial cells in MCD may indicate that these cells belong to the reservoir for HHV-8. HUM PATHOL 32:95-100. Copyright © 2001 by W.B. Saunders Company

Histopathology and molecular pathology of synovial B-lymphocytes in rheumatoid arthritis.

B-cells of the rheumatoid synovial tissue are a constant part of and, in some histopathological subtypes, the dominant population of the inflammatory infiltrate, located in the region of tissue destruction. The pattern of B-cell distribution and the relationship to the corresponding antigen-presenting cells (follicular dendritic reticulum cells: FDCs) show a great variety. B-cells may exhibit (i) a follicular organization forming secondary follicles; (ii) follicle-like patterns with irregularly formed FDC networks, and (iii) a diffuse pattern of isolated FDCs. Molecular analysis of immunoglobulin VH and VL genes from human synovial B-cell hybridomas and synovial tissue demonstrates somatic mutations due to antigen activation. The FDC formations in the synovial tissue may therefore serve as an environment for B-cell maturation, which is involved in the generation of autoantibodies. An autoantibody is defined as "pathogenic" if it fulfills the Witebsky-Rose-Koch criteria for classical autoimmune diseases: definition of the autoantibody; induction of the disease by transfer of the autoantibody; and isolation of the autoantibody from the disease-specific lesion. B-cells from rheumatoid synovial tissue show specificity for FcIgG, type II collagen, COMP, sDNA, tetanus toxoid, mitochondrial antigens (M2), filaggrin and bacterial HSPs. The contributions of these antigens to the pathogenesis of RA are still hypothetical. A possible contribution could derive from crossreactivity and epitope mimicry: due to crossreaction, an antibody directed originally against a foreign infectious agent could react with epitopes from articular tissues, perpetuating the local inflammatory process. The characteristic distribution pattern, the localisation within the area of tissue destruction, the hypermutated IgVH and IgVL genes, and their exclusive function to recognize conformation-dependent antigens suggest a central role for B-cells in the inflammatory process of rheumatoid arthritis. Therefore, the analysis of synovial B-cell hybridomas and experimental expression of synovial IgVH and IgVL genes will help to characterise the antigens responsible for the pathogenesis of rheumatoid arthritis.

The benign cystic lymphoepithelial lesion of the parotid gland is a viral reservoir in HIV type 1-infected patients.

The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.

Characteristic Proliferations of Reticular and Dendritic Cells in Angioimmunoblastic Lymphoma

Angioimmunoblastic lymphoma (AIL) is a T-cell proliferation with a distinct clinical presentation that often poses a difficult diagnostic challenge. Angioimmunoblastic lymphoma is characterized by prominent vascular and stromal proliferations. Using a panel of antibodies, we investigated the nature of the stromal component in 15 cases of AIL as compared with 40 cases of nodal-based peripheral T-cell lymphoma (PTCL) of other types. As has been previously noted, extrafollicular proliferations of follicular dendritic cells (detected by CD21 and low molecular-weight nerve growth factor receptor staining) were highly associated with AIL and were only rarely seen in other lesions. Unexpectedly, large networks of desmin-positive reticulum cells also were noted in all cases of AIL evaluated. These cells with characteristic long cytoplasmic processes were present in much smaller numbers or only rarely in other types of peripheral T-cell lymphoma. This population of nodal stromal cells, a subset of the fibroblastic reticulum cells detected by vimentin immunostaining, may be responsible for the prominent reticulum deposition seen in AIL. No association of AIL with proliferations of other types of reticulum cells (e.g., interdigitating dendritic cells or histiocytes) was noted. These findings suggest that networks of follicular dendritic and desmin-positive reticulum cells are useful diagnostic features in angioimmunoblastic lymphoma and probably are related to the pathogenesis of this entity.

Inflammatory Pseudotumor of the Liver

We describe an "inflammatory pseudotumor" of the liver that, which on detailed investigation, proved that the spindle-cell component of this lesion is derived from follicular dendritic reticulum cells (FDRC). This contention is supported by morphologic observations and by immunophenotype. The FDRC population contain Epstein-Barr virus (EBV). It is known that FDRC express the EBV receptor CD21. In this particular case, the FDRC contained clonal EBV genomes, EBV RNA (EBER) transcripts, and expressed EBV latent membrane protein (LMP1). DNA sequencing of PCR products showed three point mutations compared with the standard LMP1 sequence of the EBV strain B95-8. The findings in this case corroborate those of other investigators concerning the possible role of EBV in the development of some inflammatory pseudotumors, including the recent production of functionally active EBV-transformed FDRC-like cell lines. This association could prove instructive in delineating the histogenesis of these tumors and further assist in making prognostic and therapeutic decisions.

Immunohistochemical analysis of proliferating and antigen-presenting cells in rheumatoid synovial tissue.

We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n = 21). The immunohistochemical detection of the proliferation-associated antigen Ki67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD68) antigen. Ki67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21). Ki67-positive T lymphocytes could be detected in T-lymphocyte aggregates (8/21), in the vicinity of blood vessels (18/21) and within the enlarged synovial intima (15/21). Semiquantitative analysis showed a strong correlation between the numbers of Ki67-positive B lymphocytes and FDCs and between the numbers of Ki67-positive T lymphocytes and interdigitating dendritic reticulum cells (IDC). There were significant differences in the number of Ki 67-positive B and T lymphocytes, IDCs and FDCs between the two groups of rheumatoid arthritis (RA) patients with different local clinical activity. These findings demonstrate a low proliferation of SLCs with and without expression of the monocyte-specific antigen Kim 8 and imply that B and T lymphocyte proliferation occurs in the presence of FDCs and IDCs. These results indicate that the RA synovial tissue is a site for antigen-dependent proliferation and maturation of B and T lymphocytes. The atypical pattern of FDC distribution within the rheumatoid synovial tissue "dysmorphic follicle" may be regarded as morphological substrate for a dysmaturation compartment of B lymphocytes leading to pathogenetic autoimmune phenomena in RA patients.

Diagnosis of Castleman's disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies.

Castleman's disease (CD) is characterized by lymph node enlargement due to hyperplasia of abnormal lymphoid follicles and paracortical lymphocytic hyaline vascular (HV) stroma or plasmacytosis (PC). The lymphoid follicles in CD show involuted germinal centers and prominent mantle zone lymphocytes. Ninety-seven cases clinically suspected to be CD were analyzed according to conventional histologic criteria established by Castleman and Keller for diagnosis. Twenty-two cases were excluded as nonspecific hyperplasia (12); Hodgkin's and non-Hodgkin's lymphoma (9); and multiple myeloma involving lymph node paracortex (1). The 75 remaining cases, consisting of 51 cases of CD and 24 with altered follicles or paracortex suggestive of CD, were further analyzed immunohistologically for changes in follicular dendritic reticulum cells (FDRC) using the monoclonal antibody Ki-M4p, for germinal center proliferation with Ki-S5, for mantle zone immunophenotype with Ki-B3 and Ki-B5, for paracortical plasmacytoid monocytes with Ki-M1p, and for plasma cell clonality by applying antibodies to kappa and lambda immunoglobulin light chains. Lymph nodes showing nonspecific follicular and paracortical hyperplasia were included as controls. Hyaline vascular CD and plasma cell CD showed enlarged, polyploid FDRC with prominent nucleoli, decreased germinal center proliferation, and mantle zone populations of immunophenotypically aberrant, Ki-B3-negative B lymphocytes. Thirty-seven percent of hyaline vascular CD and plasma cell CD contained plasmacytoid monocytes, and 15% showed interstitial areas of lambda predominant plasma cells. Plasmacytoid monocytes were common in hyaline vascular CD but rare in plasma cell CD. Cases suspected to be CD that demonstrated a mantle zone population of Ki-B3-negative B lymphocytes had clinical finding of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, and skin changes or sclerotic bone lesions) syndrome and were reclassified as hyaline vascular CD, plasma cell CD, and mantle zone CD with an aberrant mantle zone immunophenotype only (lacking follicular center and paracortical histologic or immunohistologic abnormalities). Immunohistochemistry was valuable for identification of dysplastic FDRC, decreased germinal center proliferation, and plasmacytoid monocytes. In addition, immunohistochemistry was essential for detection of plasma cell clonality, an aberrant mantle zone immunophenotype, and mantle-zone-restricted CD that was devoid of diagnostic alterations of germinal center or paracortex.

Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease

Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease

Pathology of Hodgkin's disease.

This review addresses several current questions about Hodgkin's disease (HD): 1) Does HD represent a single disease or multiple diseases? 2) What is the role of cytokines in HD? 3) What is the nature of the Reed-Sternberg cell? 4) How are Epstein-Barr virus (EBV) and oncogenes (bcl-2, c-myc, and p53) involved in the pathogenesis of HD? Nodular lymphocyte predominance HD appears to be a distinct clinicopathologic entity. Cytokines attract inflammatory cells, induce fibrosis, upregulate oncogenes and adhesion molecules, cause systemic symptoms, and mediate immune suppression. Reed-Sternberg cells are derived from B and T lymphocytes in most instances, although an alternative origin from a follicular dendritic reticulum cell has been proposed. EBV is an etiologic agent in some but not all HD cases. EBV gene products confer a growth advantage on Reed-Sternberg cells. The bcl-2 and p53 oncogenes protect Reed-Sternberg cells from apoptosis and are not directly upregulated by EBV.

Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte aggregates in Sjogren's syndrome and rheumatoid arthritis.

Interactions between vascular cell adhesion molecule 1 (VCAM-1) and its ligand, the alpha 4/beta 1 integrin, have been shown to be important in a number of cellular events in vitro. To assess the importance of such interactions in the development of lymphocytic infiltration in diseased tissue the distribution of the two ligands has been studied immunohistochemically. Cryostat sections of labial tissue from patients with Sjögren's syndrome, normal labial tissues, rheumatoid synovia, and normal tonsils were stained using antibodies to VCAM-1, alpha 4 and beta 1 integrin chains, and markers for T cells, B cells, macrophages, and follicular dendritic reticulum cells (FDRCs), visualised using alkaline phosphatase and fast red. Staining patterns for VCAM-1 and integrin chains in lymphocyte aggregates in synovial and labial tissues were similar. VCAM-1 staining was found on both vascular and ramifying dendritic cells at the centre of large T cell aggregates and in all aggregates where there was a central clustering of B cells. VCAM-1 colocalised with, but also extended beyond, staining for the FDRC marker R4/23. Staining for the alpha 4 and beta 1 integrin chains was more widespread than staining for VCAM-1, with no significant increase in staining at sites of maximum VCAM-1 staining. In tonsils VCAM-1 and R4/23 codistributed in germinal centres, but staining for the alpha 4 and beta 1 integrin chains was chiefly seen in T lymphocyte areas. VCAM-1 may be more important in determining the distribution of B than T lymphocytes in lymphocytic infiltration of non-lymphoid tissue. Unlike the follicles of lymphoid tissue, ectopic follicle-like structures in non-lymphoid tissues may form by immigration of B cells via VCAM-1+ vessels at the centre of T cell aggregates.

Expression of interleukin-6 in Castleman's disease

Although mixed forms of Castleman's disease (CD) may occur, two classically recognized forms are the angiofollicular (hyaline vascular [V]) variant and the plasma cell (P) variant. The two forms of CD differ greatly in their clinical and histopathologic manifestations. Plasma cell CD is characterized by the presence of hyperplastic germinal centers (GCs) and sheets of plasma cells in the interfollicular areas. In this study we demonstrated an abundant expression of interleukin-6 (IL-6) in most GC B cells and in the numerous immunoblastoid B cells in the mantle zone and interfollicular areas in CD-P. Patients with CD-P also have an elevated serum IL-6 level. The increased IL-6 production is responsible for the marked plasma cell infiltration in lymph nodes and bone marrow as well as for the elevated gammaglobulin level in serum. In contrast, CD-V is distinguished by the presence of atrophic GCs, which often are populated by cytologically atypical follicular dendritic reticulum (FDR) cells, as well as by sheets of T-zone plasmacytoid histiocytes and increased numbers of capillaries in the interfollicular areas. In contrast to the findings in CD-P, we did not observe significant expression of IL-6 in GC cells or in immunoblastoid cells in CD-V; this may account for the paucity of plasma cells in this form of CD. The reason for the atypical changes in FDR cells as well as the increases in T-zone plasmacytoid histiocytes and capillaries seen in CD-V are not known inasmuch as no cytokines, such as IL-1, IL-4, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor, were detectable in tissues. It is possible that in CD-V the atypical change in FDR cells could lead to a disturbance of B-lymphocyte/FDR cell interaction and subsequently to poor development of GCs. The study clearly indicates that the histopathologic and clinical features of CD vary greatly depending on the capacity of activated B cells to produce IL-6. However, lack of IL-6 secretion by GC cells alone cannot explain the histopathologic alterations in CD-V.

The Central Role of Follicular Dendritic Cells in Lymphoid Tissues

Publisher Summary This chapter discusses the role of follicular dendritic cells in lymphoid tissues. Characteristic features of primary and secondary lymphoid follicles are follicular dendritic cells (FDCs) that are not found in any other human organ. FDCs were first described as a nonlymphoid population of embryonic nonphagocytic reticulum cells. Other names for FDCs have been used in the past, for example, dendritic reticulum cells (DRCs), follicular dendritic reticulum cells, antigen-retaining reticular cells, follicular antigen-binding dendritic cells, and dendritic macrophages. FDCs are considered as having a passive role in the function of the germinal center. It is characterized as nonphagocytic cells that capture and retain complexes of antigen, antibodies, and C3 on their cell surface. By expressing antigen–antibody complexes and a large number of cell–cell and cellmatrix molecules, FDCs were shown to regulate normal B cell function. There is growing evidence that FDCs could be important constituents of the malignant counterpart of the germinal center. In addition, FDCs were demonstrated to be the target cells in human immunodeficiency virus (HIV)-related lymphadenopathy. These data can be integrated into a concept of FDCs as the key component of the germinal center microenvironment. FDCs demonstrate a unique antigen pattern by co-expressing myeloid and B cell markers.