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PubMed1987

Expression of CR1 and CR2 complement receptors following Epstein-Barr virus infection of Burkitt's lymphoma cell lines.

Epstein-Barr virus (EBV) infection of human B lymphocytes involves a specific receptor closely associated with, or identical to, the C3d complement receptor, CR2. Thus, 25 out of 29 EBV-positive Burkitt's lymphoma (BL) cell lines but none of 15 EBV-negative BL lines were found to express C3 receptors. Furthermore, in vitro infection with EBV of six EBV-negative cell lines resulted in the expression of C3 receptors in association with that of EBV-determined nuclear antigen (EBNA). Rosette assays using erythrocytes coated with human C3b, C3bi, and C3d, inhibition of rosette formation with anti-receptor antibodies, and flow cytometry analysis of stained cells demonstrated that EBV-converted lines expressed C3b and C3d receptors, CR1 and CR2. Anti-receptor antibodies recognized an average of 40,700 anti-CR1 and 140,000 anti-CR2 binding sites on an EBV-converted line (BL41/B95), whereas no specific binding occurred on the corresponding EBV-negative (BL41) cells. Because CR1 and CR2 are involved in B-cell proliferation and/or differentiation, enhanced expression of C3 receptors following the interaction between EBV and B cells and/or subsequent infection of the cells by EBV may provide a basis for positive control of B lymphocyte proliferation by EBV.

B-Lymphocytes↗
PubMed1987

Influence of processing by erythrocyte C3b/C4b receptors (CR1) on binding of immune complexes to Raji cells and polymorphonuclear granulocytes.

The binding of 125I-labelled bovine serum albumin (BSA)-anti-BSA immune complexes (IC) to Raji cells and polymorphonuclear (PMN) cells in vitro was studied. The IC were reacted for 1 h at 37 degrees C with normal human serum (NHS) diluted 1:2 in the presence or absence of human erythrocytes (E) before presentation for Raji cells or PMN cells. The IC showed a two to three fold increased binding to C3d, g receptors (CR2) on Raji cells, when E-CR1 had been present during the reaction with NHS, compared to IC similarly reacted with NHS only. Blocking of the E-CR1 by a polyclonal anti-CR1 antibody reduced the subsequent binding of IC to Raji cells to the same level as that obtained with IC reacted with serum only. Binding to PMN granulocytes of IC reacted with NHS in the presence of E-CR1 showed a 60% reduction compared to the binding of IC reacted with NHS only. It is concluded that interaction of complement-reacted IC with CR1 on erythrocytes leads to a more efficient generation of CR2-binding C3d, g-containing IC with reduced reactivity to PMN cells.

Animals↗
PubMed1993

Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV.

Complement activation by HIV results in the binding of C3 fragments to the gp160 complex and enhanced infection of C3 receptor-bearing target cells. We have studied complement-mediated enhancement of infection of the human CD4-positive T-cell line HPB-ALL which expresses the CR1 (CD35) and CR2 (CD21) receptors for C3. CR1 and CR2 are present on 15% and 40% of normal peripheral blood CD4-positive T lymphocytes respectively. Opsonization of the virus with complement resulted in a 3- to 10-fold enhancement of infection of HPB-ALL cells, as assessed by measuring the release of p24 antigen in culture supernatants throughout the culture period. Blockade of CR2 with cross-linked anti-CR2 monoclonal antibodies decreased infection to the level observed with unopsonized virus. Blocking CR1 reduced complement-mediated infection by 50-80%. Experiments using serum deficient in complement factor I demonstrated that CR1 mediates the interaction between opsonized virus and T cells in addition to its ability to serve as a cofactor for the cleavage of C3b into smaller fragments that interact with CR2. A requirement for CD4 in complement-mediated enhancement of infection was observed with HIV-1 Bru but not with HIV-1 RF. Thus, CR1 and CR2 contribute in an independent and complementary fashion to penetration of opsonized virus into complement receptor-expressing T cells. Involvement of CD4 in infection with opsonized virus depends on the viral strain.

CD4 Antigens↗
PubMed2006

Role of dendritic cells in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic inflammatory and lymphoproliferative autoimmune disease of unknown aetiology. It is characterised by progressive mononuclear cell infiltration of the salivary and lacrimal glands and a decreased glandular secretion, resulting in dryness of the mouth and eyes (xerostomia and keratoconjunctivitis sicca, respectively). Dendritic cells (DC) are considered to be the most potent antigen-presenting cells. Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells might lead to the break of peripheral tolerance and initiation of immune responses to self-antigens. This review will focus on the possible role of DC in SS.

Animals↗
PubMed1984

p69,71 antigen complex detected by monoclonal antibody Leu 1 in the identification of particular stages of malignant B-cell differentiation.

Lymphomatous cell samples from 86 patients with B-cell neoplasia (34 chronic lymphocytic leukaemia, 8 hairy-cell leukaemia, 5 prolymphocytic leukaemia, 20 immunocytic lymphoma, 9 centrocytic lymphoma, 3 centroblastic/centrocytic lymphoma, 3 lymphoblastic lymphoma, 1 plasma cell leukaemia and 3 plasmacytoma) were studied using the monoclonal antibody Leu 1, detecting a p69,71 antigen complex present on nearly all thymocytes, most (greater than 85%) peripheral T-lymphocytes as well as some malignant B-cells. Furthermore, we compared the reactivity of Leu 1-positive B-cells with those exhibiting conventional surface markers such as mouse-erythrocyte-receptor, FcIgG-receptor, C3b- or C3d-receptor and surface immunoglobulins of the various heavy- and light-chain types. Our results demonstrate a correlation between the expression of p69,71 antigen complex and distinct phenotypes revealed by conventional markers and underline the value of Leu 1 monoclonal antibody in the differential diagnosis of human B-cell neoplasia.

Antibodies, Monoclonal↗
PubMed1984

In situ characterization of cell infiltrates in human dental periapical granulomas. 2. Demonstration of receptors for the complement components C3b and C3d.

The inflammatory cell infiltrates in human dental periapical granulomas were studied through the demonstration of receptors (R) for fragments C3b and C3d of the complement component C3, C3bR and C3dR were detected in cryostat sections by the closed chamber hemadsorption technique. Sheep erythrocytes sensitized with rabbit IgM antibody and coated with human C3B or C3d were used as indicator cells. Of the 62 granulomas studied, 23 showed strong or moderate C3bR activity, and weak C3dR activity was detected in 5 out of 25 specimens. The C3bR activity was abolished by treatment with 0.25 mM periodic acid, indicating that carbohydrate is a part of the C3bR. Using an antiserum to C3R as first layer in indirect immunofluorescence experiments, the C3R was localized to cell membranes. The low C3dR activity indicates that a minor part of the mononuclear cells in the human periapical granulomas were B lymphocytes.

Adult↗
PubMed1982

The ontogeny of immunological receptors in the thymus.

Receptors for sheep erythrocytes, for the Fc part of IgG (Fc gamma R) and IgM (Fc mu R), and for components of activated human complement C3 (C3bR and C3dR) in thymus tissue from fetuses, infants and children were studied using haemadsorption to cryostat sections in a closed chamber. Sheep erythrocytes (SE) did not adhere to sections of thymus from fetuses at 10-11 weeks of gestation, adhered weakly between 14 and 20 weeks, while they adhered in a dense monolayer in older fetuses, in infants and in children, denser in the cortex than in the medulla. Ox erythrocytes (OE), sensitized with IgG to demonstrate Fc gamma R, adhered focally to both cortical and medullary areas. The adherence was more pronounced to the sections of fetal thymus than to the sections from infants and children. OE, sensitized with IgM to demonstrate Fc mu R, adhered focally to all thymus tissue sections, preferentially to the cortex. The adherence was most pronounced in fetal thymus. SE, sensitized with IgM and coated with complement, adhered to sections of fetal thymus, but the density decreased markedly during fetal life. Indicator cells demonstrating C3bR adhered focally also to sections from infants and children, while indicator cells demonstrating C3dR did not adhere to sections from individuals older than 38 weeks of gestation. Indicator cells demonstrating C3bR and C3dR adhered both to cortex and medulla.

Animals↗
PubMed1989

Enhanced binding of immune complexes processed by erythrocyte CR1 (CD 35) receptors to purified CR2 (CD 21) receptors from tonsillar mononuclear cells.

The binding of immune complexes (IC) opsonized by serum complement (C) and IC processed by CR1 (CD 35) receptors on human erythrocytes (E) to purified CR2 (CD 21) receptors was compared. Soluble CR2 was prepared from tonsillar mononuclear cells and purified by antibody affinity chromatography. Solid phase CR2 as well as CR2 subjected to PAGE and blotted onto nitro-cellulose membranes bound 125I-labelled BSA anti-BSA IC which had been opsonized by C and processed by CR1 up to ten times more efficiently than IC reacted with serum only. Radiolabelled monomeric C3d also bound to solid phase CR2. The binding of IC to purified and solid phase bound CR2 could be inhibited by anti-CR2 antibodies or by preincubation of the IC with polyclonal antibodies reacting with C3d or C3b/iC3b. Thus, both C3dg and iC3b appeared to mediate binding of IC to CR2. Preincubation of solid phase CR2 with purified monomeric C3d did not inhibit the subsequent binding of E-CR1 processed IC. The data indicate that E-CR1 have an important role in generating IC which bind effectively to CR2 receptors on B lymphocytes.

Animals↗
PubMed1998

Dependence of germinal center B cells on expression of CD21/CD35 for survival.

Affinity-driven selection of B lymphocytes within germinal centers is critical for the development of high-affinity memory cells and host protection. To investigate the role of the CD21/CD35 coreceptor in B cell competition for follicular retention and survival within the germinal center, either Cr2+ or Cr2null lysozyme-specific transgenic B cells were adoptively transferred into normal mice immunized with duck (DEL) or turkey (TEL) lysozyme, which bind with different affinities. In mice injected with high-affinity turkey lysozyme, Cr2null B cells responded by follicular retention; however, they could not survive within germinal centers. This suggests that CD21 provides a signal independent of antigen that is required for survival of B cells in the germinal center.

Adoptive Transfer↗
PubMed1985

Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b.

It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. albicans and C. stellatoidea, not to other species pathogenic to humans. There was evidence of a lectinlike nature of the effect.

Animals↗
PubMed1990

Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans.

Pseudohyphae of Candida albicans bear surface receptors for iC3b and C3d. In order to determine a possible role for these receptors in the pathogenesis of candidiasis, a spontaneous C. albicans mutant, m-10, which exhibits reduced ability to adhere in vitro to fibrin platelet clots and epithelial cells or to cause endocarditis in a rabbit model, and its parent wild-type (wt) strain were compared for receptor expression in rosetting assays with sheep erythrocytes carrying iC3b (EAC1423bi) or C3d (EAC1423d). An equally high attachment to wt and m-10 was seen with EAC1423d, whereas rosetting with EAC1423bi was reduced by 53% in m-10 compared with wt. In inhibition studies, rosetting of wt with EAC1423bi was markedly inhibited by culture filtrate, hyphal-cell extract, and DEAE-fractionated material prepared from wt (54, 87, and 70% decreases in rosetting, respectively), thus suggesting the presence of the soluble, functionally active iC3b receptor of C. albicans in each of these preparations. Minimal inhibition of iC3b rosetting, however, was seen with the identical materials from m-10 (21, 5, and 12%, respectively). All of the preparations from the two strains were equally effective in their inhibitory activities against rosetting of C3d. A human serum specimen obtained from a patient with chronic mucocutaneous candidiasis blocked iC3b rosetting of the wt strain almost completely. When used in an immunoblot, this serum recognized proteins of 68 to 71, 55, and 50 kilodaltons (kDa) in hyphal-cell extracts of the wt. With the same preparation of the avirulent mutant, only weak reactions with the 68- to 71-kDa and 55-kDa proteins occurred, while the 50-kDa protein was not detectable. Taken together, these results indicate that the expression of the functionally active iC3b receptor on C. albicans may be involved in the virulence of the organism, possibly by mediating adherence to mammalian cells.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2006

Optimal long-term humoral responses to replication-defective herpes simplex virus require CD21/CD35 complement receptor expression on stromal cells.

Replication-defective herpes simplex virus (HSV) strains elicit durable immune responses and protect against virulent HSV challenge in mice, despite being unable to establish latent infection in neuronal cells. Mechanisms for generating long-lived immunity in the absence of viral persistence remain uncertain. In animals immunized with replication-defective HSV, durable serum immunoglobulin G (IgG) responses were elicited. Surprisingly, Western blot analyses revealed that the specificities of antiviral IgG changed over time, and antibody reactivity to some viral proteins was detected only very late. Thus, some of the durable IgG activity appeared to be contributed by either new or significantly enhanced antibody responses at late times. Following immunization, radiation bone marrow-chimeric mice lacking complement receptors CD21 and CD35 on stromal cells elicited only short-lived serum IgG and failed to mount recall responses to subsequent HSV exposure. Our results suggest that complement-mediated retention of viral antigens by stromal cells, such as follicular dendritic cells, is critical for optimal maintenance of antibody responses and B-cell memory following vaccination with replication-defective HSV.

Animals↗
PubMedDate not supplied

Follicular dendritic cell tumor of the cervical lymph node.

Follicular dendritic cell (FDC) tumor is an uncommon sarcoma, which occurs in lymph nodes or in extranodal sites. A 61-year-old female was referred to our hospital because of a nontender mass on her neck. The mass was surgically removed and initially diagnosed as a metastasis of malignant fibrous histiocytoma (MFH). Because the subsequent progress was inconsistent with the common prognosis of a patient with MFH, the possibility of FDC tumor was taken into consideration. Immunohistological studies for FDC antigens, such as CD21 and CD35, led to final diagnosis. It is suggested that FDC tumor should be included in the diagnostic considerations when a spindle cell tumor is present in a lymph node.

Antigens, CD↗
PubMed2003

Role of complement in the development of autoimmunity.

B cell complement receptors have been shown to be important in the generation of normal humoral immune responses, and they likely also participate in the development of autoimmunity. Complement component and receptor deficiencies have been associated with SLE in both animal models and patients with disease. Recent data suggest that Cr2 is a lupus susceptibility gene in the NZM2410 mouse model for lupus, as it generates complement receptors that are structurally and functionally altered. Complement deficiency may result in autoimmune disease because of the inability to appropriately clear immune complexes or apoptotic cells or by the impaired generation of C3-coated autoantigens for CR1/CR2. In turn, CR1/CR2 may participate in the maintenance of B cell tolerance by lowering the threshold for negative selection of autoreactive B cells, by targeting autoantigen to FDCs in secondary lymphoid organs, or by regulating autoreactive T cell function. The effect of CR2 has not been dissected from that of CR1 in the animal studies performed to date. Furthermore, the effects of CR1/CR2 dysfunction or partial deficiency, which are found in the NZM2410 mouse model and in patients with SLE respectively, have not been delineated from those of complete deficiency, which has been studied in several animal models of autoimmunity and tolerance. Although CR1/CR2 dysfunction or deficiency may confer only a modest phenotype in isolation, it is likely that when combined with other disease susceptibility genes it will result in a fully penetrant end-stage disease phenotype. Understanding the mechanisms by which these receptors participate in the maintenance of B cell tolerance will be critical in developing appropriate therapeutic interventions for patients with autoimmune diseases such as SLE.

Animals↗
PubMed1982

A comparative evaluation of receptor reactivities for C3b, iC3b, and C3d on Raji lymphoblastoid cells.

Raji cells were described to carry receptors for iC3b, C3d, C3b-beta 1 H and beta 1 H. Controversial opinions, however, exist whether or not these cells carry also receptors for C3b. Using highly purified C3, definitely devoid of beta 1 H and C5, for preparation of C3b intermediates, it could be shown that Raji cells bound to C3b cells. Furthermore, Raji cells reacted with monoclonal antibodies that interfered with binding of C3b to human erythrocytes, lymphocytes and renal cells. The receptor for C3b on Raji cell, however, exhibited some special properties and, therefore, required some distinct experimental conditions for its detection: (1) The origin of the erythrocytes used for preparation of the C3b intermediates seemed to be important; this was not the case when iC3b and C3d receptor reactivity was assessed. (2) Rosettes already formed between Raji cells and EAC1423b showed the tendency to disintegrate within the first 30 min after the rosette formation assay. Again, this effect could not be observed with iC3b- and C3d-dependent rosette formation. (3) Incubation of the Raji cells at 37 degrees C as well as 4 degrees C before rosette formation resulted in a rhythmic loss and reappearance of C3b receptor reactivity. At room temperature (19-22 degrees C) this effect was much less expressed. There was no influence of preincubation at 4 and 37 degrees C, respectively, on the iC3b and C3d receptor reactivity of Raji cells. (4) Diisopropylfluorophosphate (DFP) present during rosette formation enhanced, within a certain range of concentration, the percentage of C3b-dependent rosette formation. iC3b and C3d receptor reactivity was not influenced. A similar reaction pattern was observed with pokeweed mitogen (PWM)-stimulated tonsil lymphocytes. In the concentrations tested, DFP showed no effect on the rosette formation between C3b, iC3b, and C3d cells, respectively, and unstimulated tonsil lymphocytes. The data presented suggest that C3b receptors on Raji cells undergo some special metabolism, possibly controlled by fluid phase or cell-bound proteases. This might be a common property of C3b receptors on blast-like and transformed cells, differing from that of unstimulated small lymphocytes.

Binding Sites, Antibody↗
PubMed1991

Expression of complement receptor CR2 (CD21) on human subcorneal keratinocytes in normal and diseased skin.

Human keratinocytes are able to synthesize and express cell surface moieties characteristic of effector and/or accessory cells of the immune system (CD16, CD36, HLA-DR, intercellular adhesion molecule-1). In the present study, skin biopsies from healthy volunteers, from patients with psoriasis vulgaris (PV), mycosis fungoides (MF), purpura pigmentosa chronica (PPC), acute urticaria (AU) and from positive tuberculin skin tests were investigated with regard to the reactivity with the monoclonal antibodies to complement receptors CR1 CR2 and CR3 by means of a multistep immunoperoxidase method. In the clinically involved skin of all patients with PV, MF or PPC, and in biopsies obtained from positive tuberculin tests, specific epidermal intercellular staining with OKB7 and Leu anti-CR2 was seen on subcorneal keratinocytes. This finding suggests a differentiation-linked expression of CR2 on human keratinocytes in cytokine-mediated skin diseases whereas CR1 and CR3 are apparently not expressed.

Antigens, CD↗
PubMedDate not supplied

Intraabdominal follicular dendritic cell sarcoma: report of a case with fine needle aspiration findings.

BACKGROUND: Follicular dendritic cell sarcoma is a rare tumor derived from dendritic cells of lymphoid follicles. Although it shows characteristic cytologic, histologic and immunohistochemical features, it may be misdiagnosed because of the lack of experience with this entity. There are few reports in the cytologic literature describing this entity. CASE: A left hypochondrial mass was found in an 80-year-old man who had a past history of colonic carcinoma. A computed tomography-guided fine needle aspiration biopsy was performed, and the findings were initially thought to be compatible with metastatic carcinoma. The mass was excised, and a diagnosis of follicular dendritic cell sarcoma was made. CONCLUSION: Follicular dendritic cell sarcoma is characterized by loosely cohesive or syncytial groups of dendritic cells that show oval, vesicular nuclei and ill-defined cytoplasm intimately admixed with small, mature lymphocytes. The diagnosis can be confirmed by positive immunostaining for CD21 and CD35 antigens and negative staining for cytokeratin. Unusual features in our case were the presence of prominent plasma cells and intracytoplasmic, periodic acid-Schiff stain, diastase-positive deposits, with the last not described before.

Aged↗