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At least 325 records · Page 18Linked to original sources
PubMed2000

Binding of the Epstein-Barr virus major envelope glycoprotein gp350 results in the upregulation of the TNF-alpha gene expression in monocytic cells via NF-kappaB involving PKC, PI3-K and tyrosine kinases.

Epstein-Barr virus (EBV) is a human herpesvirus that interacts with various immunocompetent cells that carry the EBV receptor (CD21/CR2). EBV binds to CR2 through its major envelope glycoprotein 350 (gp350). Previously we had demonstrated that EBV and other human herpesviruses are capable of modulating cytokine synthesis through the deregulated expression of cytokine genes interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2). Here we show that, in contrast to infectious EBV, purified recombinant gp350 upregulates TNF-alpha gene expression in human monocyte/macrophages (M/M) as well as in a monocytoid cell line, U937. Our results also demonstrate that this increased expression is due to both enhanced transcription and stability of TNF-alpha mRNA in gp350-treated cells. The specificity of this effect is evidenced by the fact that pre-incubation of cells with anti-CR2 monoclonal antibody OKB7, which blocks binding of gp350 to CR2, inhibits the above mentioned effects of gp350. Furthermore, we demonstrate that activation of TNF-alpha by gp350 is mediated by NF-kappaB through signal transduction pathways involving PKC, PI3-K and tyrosine kinases. To our knowledge this is the first report describing the modulation of TNF-alpha gene expression by the EBV-gp350 molecule following its interaction with the viral receptor CR2 on cells of the monocytic lineage.

Antibodies, Monoclonal↗
PubMed1998

CD21/CD35 in B cell activation.

The stimulus induced via the B cell receptor is a major factor in determination of the fate of naive B cells resulting in activation, elimination or anergy. The strength of B cell signal transduction is dependent not only on the affinity of antigen binding, but by positive signals via the co-receptor CD21/CD19/Tapa-1. Absence of CD21 expression by B cells results in an impaired humoral response to T-dependent antigens which is characterized by a reduction in B cell follicular retention and germinal center survival. The ligand for CD21 is complement C3d which becomes attached to antigen on activation of the complement system. Thus, the complement system of innate immunity is an important regulator of B lymphocytes.

B-Lymphocytes↗
PubMed2001

Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor function.

The initiation of antibody responses to foreign antigens requires that B cells receive and integrate a variety of signals through an array of cell surface receptors including the B cell antigen receptor (BCR) as well as a number of essential coreceptors. Recent evidence indicates that cholesterol-rich plasma membrane microdomains, referred to here as lipid rafts, serve as platforms for BCR signaling and trafficking in B cells. The existence of rafts suggests a previously unappreciated level of organization at the B cell surface that may explain, at least in part, how BCR signaling is coordinated. Here the current evidence that lipid rafts play a key role in B cell responses is reviewed.

Antigens↗
PubMed1993

Epstein-Barr virus gene expression in oral hairy leukoplakia.

A combination of Northern blotting and sequencing of clones from a cDNA library constructed using RNA isolated from oral hairy leukoplakia (OHL) has been used to study Epstein-Barr virus (EBV) gene expression in this AIDS-associated lesion, the only accessible source of in vivo-replicating EBV. Because of the limited amount of RNA available, Northern blotting was only useful for detection of very abundant EBV transcripts in the OHL biopsies. Analysis of cDNA clones containing the BdRF1, BCRF1, gp350/220, BARF0, and BKRF4 reading frames and further characterization of RNA structures spanning BCRF1 (viral IL-10) in lymphocytes infected with EBV has provided a preliminary comparison of some virus replicative gene expression in its two main host cell types. No expression of EBNA-1, EBNA-2, or EBNA-3A RNA was detected in the oral hairy leukoplakia cDNA library.

Animals↗
PubMed1997

Differential effects on HIV-1 gene regulation by EBV in T lymphocytic and promonocytic cells transduced to express recombinant human CR2.

A panel of human hematopoietic cell lines was genetically engineered to express recombinant complement receptor 2 (CR2 or CD21), which is also the Epstein-Barr virus (EBV) receptor. The panel was composed of SupT1, J1.1, and U1.HIV cells. The latter is a promonocytic cell line, whereas the other two are T lymphocytic cell lines. J1.1 and U1.HIV cells are latently infected by human immunodeficiency virus type 1 (HIV-1). These three cell lines were transduced with a murine leukemia virus (MLV)-based retroviral vector system. CR2 was efficiently and consistently expressed on the cell membranes, conferring enhanced susceptibility to EBV infection. The efficient expression of recombinant CR2 in cell lines of hematopoietic origin allowed for study of the interaction between EBV infection and HIV-1 gene regulation in suitable cell-culture models. The effects of EBV and HIV-1 coinfection results were cell-type dependent. In the two T lymphocytic cell lines, HIV-1 expression was rapidly and persistently down-regulated by EBV. Conversely, in the promonocytic cell line U1.HIV-CR2, HIV-1 expression was transiently enhanced by EBV. The EBV and HIV-1 coinfection result in U1.HIV-CR2 cells is potentially important, as the activation of HIV-1 gene expression in monocyte-like cells may play a crucial role in the mechanism of CD4+ T cell depletion by apoptosis. Therefore, the U1.HIV-CR2 cell line may represent a useful cell-culture system to study the synergism between EBV and HIV-1 in inducing apoptosis in primary CD4+ T cells.

Cell Line↗
PubMed2000

Patterned entry and egress by Epstein-Barr virus in polarized CR2-positive epithelial cells.

In polarized epithelium direction of viral entry and release correlates with proclivity of a virus to establish local versus systemic infection. The Epstein-Barr virus (EBV), whose principal tissue reservoir is B lymphocytes, also has disease manifestations in epithelium, suggesting intertissue spread potentially influenced by epithelial cell polarity. We stably transfected the B lymphocyte EBV receptor (CR2/CD21) into Madin-Darby canine kidney (MDCK) epithelial cells used extensively to study effects of cell polarity on infection by both DNA and RNA viruses. CR2/CD21 was detected on both apical and basolateral surfaces of polarized MDCK cells, with predominant expression basolaterally. However, infectivity was up to four-fold greater apically, suggesting that endogenous cell surface molecules, sorted asymmetrically onto polarized plasma membranes, may be involved in EBV entry into MDCK cells. EBV gp350/220, a replicative cycle glycoprotein added to the virus envelope on egress through the cell membrane, was immunolocalized by confocal microscopy to basolateral cell surfaces only. Apical entry of EBV with subsequent basolateral release of newly replicated virus favors systemic infection by viral dissemination to underlying lymphocytic aggregations. Under conditions of long-term culture, latent EBV was not stably maintained in these cells, suggesting that the epithelial phase of acute EBV infection may be transient.

Animals↗
PubMed2001

Growth transformation of primary epithelial cells with a NPC-derived Epstein-Barr virus strain.

The Epstein-Barr virus (EBV) is associated with two major human epithelial malignancies, where it is likely to play a role in the malignant phenotype: undifferentiated nasopharyngeal carcinoma (100% of cases) and gastric carcinomas (about 10% of cases). We and others have obtained growth transformation of monkey kidney primary epithelial cells by transfection of viral DNA, especially with the BARF1 gene of EBV (Wei et al., 1997). We now report that the same type of primary epithelial cells can be growth-transformed using EBV particles derived from a nasopharyngeal carcinoma tumor line. Not only can these EBV-infected cells grow over 100 passages, escaping senescence, in contrast to their noninfected counterparts, but they can also survive and proliferate at very low cell density. Several subclones were characterized in terms of viral gene expression. All these clones gave a similar pattern, with detection of EBNA1 and BARF1 proteins but absence of LMP1. CD21, which is the main EBV receptor on B lymphocytes, was not expressed on parental monkey kidney epithelial cells nor on EBV-infected cell clones. This model of epithelial cell transformation will be useful for a better investigation of EBV functions critical for oncogenesis of epithelial cells.

Animals↗
PubMed2006

A minimum CR2 binding domain of C3d enhances immunity following vaccination.

The degradation product of the third (C3) complement component, C3d, links innate and adaptive immunity, and the covalent attachment of C3d to an antigen enhances antigen-specific immune responses. C3d has been hypothesized to enhance immunity by direct interaction with complement receptor 2 (CR2/CD21) on immune cells. However, the domains on C3d important for CR2 binding have been controversial, with various studies reaching contradictory conclusions. In addition, the concept of B-cell activation via CR2 by C3d has been questioned, since mice lacking CR2 still elicit C3d-enhanced immunity following vaccination. Therefore, the goal of this study was to determine if a peptide representing one of the proposed CR2 binding domains of C3d could substitute for the entire protein and enhance antigen-specific immunity. Mice (BALB/c) were vaccinated with the HIV-1 gp120 envelope glycoprotein (Env(gp120)) alone or fused to multiple copies of the murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2 binding domain. Each immunogen was expressed from DNA plasmid in vivo or injected as purified recombinant protein. The fusion of the P28 peptide to Env(gp120) enhanced both humoral and cell-mediated immune responses with similar efficiency as Env(gp120) conjugated to C3d. The fusion of C3d or P28 to Env(gp120) elicited higher-titer anti-Env specific antibody, enhanced avidity maturation of the elicited antibody, and elicited higher numbers of IFN-gamma and IL-4 secreting cells compared to Env(gp120) immunizations. This CR2-binding domain specific 28 amino acid peptide can substitute for the entire C3d molecule and enhance immunity. These results indicate that the adjuvant properties of C3d are associated with CR2 interaction.

Adjuvants, Immunologic↗
PubMed1999

CD21high IgMhigh splenic B cells enriched in the marginal zone: distinct phenotypes and functions.

Collectively, these findings suggest that MZ B cells have unique signaling and subsequent differentiative capabilities that permit them to react much more vigorously than the majority of splenic B cells (FO) in the earliest stages of an in vivo immune response. This is particularly evident with limiting T cell help, low concentration of thymus-independent mitogens or low amounts of particulate blood-borne antigen in the spleen (Fig. 4). They are uniquely situated adjacent to the marginal sinuses and a rich array of antigen trapping macrophages. Because of this location the MZ B cells are ideally positioned for immediate exposure to blood-borne antigens. In contrast, the FO B cells are in juxtaposition to the PALS which may expedite the interactions of FO B cells with T cells and antigen presenting cells. Collectively these properties point to a role for FO B cells in antibody responses to T dependent antigens generated in germinal centers. These responses occur temporally later in immune responses and may be involved principally in the response to protein antigens. [figure: see text].

Animals↗
PubMed1999

Role of complement receptors CD21/CD35 in B lymphocyte activation and survival.

In summary, the complement system has evolved an important function in regulation of humoral immunity to T-dependent antigens. Covalent attachment of activated C3 to antigen alters its fate by enhancing uptake on the surface of FDC via CD21/CD35; and by enhancing signal transduction via the B cell coreceptor CD21/CD19/Tapa-1. In the absence of complement receptors CD21/CD35 or C3 ligand, naive B cells bearing low affinity BCR fail to effectively survive within the lymphoid follicle following contact with antigen and death is mediated by a Fas-dependent mechanism. Alternatively, B cells sufficiently activated to initiate a GC reaction fail to survive in the absence of CD21-CD21L interaction.

Animals↗