Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD40, a glycoprotein expressed on B lymphocytes plays an important role in B cell development, growth and differentiation. The ligand for the CD40 is a 39-kDa glycoprotein (CD154) expressed on the surface of activated T lymphocytes and is essential for thymus-dependent humoral immunity. The expression of CD154 is tightly regulated and its transient expression reduces the chances of potentially deleterious bystander activation of B cells. Stimulation through CD40 has been studied in vitro by using antibodies against CD40, by membranes of activated T cells or lately, by CD154 transfected cells. In this work we have evaluated the outcome of CD40-CD40 ligand interaction in vitro and in vivo by using CD154-transfected L929 cells. In vitro assays showed that CD154-L929 cells can induce on B cells: IL-4-dependent proliferation, up-regulation of CD23, CD54 and class II molecules and can also rescue WEHI-231 B cell lymphoma from anti-IgM-induced apoptosis. Interestingly, in vivo assays revealed that when CD154-L929 cells were inoculated into the spleen, mice developed a strong but transient production of anti-erythrocyte autoantibodies. Through B lymphocyte activation with CD154-transfected L929 cells both in vitro and in vivo, our data reveal that enforced and prolonged expression of CD40 ligand overcomes the tightly regulated mechanisms of B cell activation, triggering the production of autoantibodies. This system might be used to evaluate the early steps of an autoimmune response and the role of CD40-CD154 in the induction of primary responses in vivo.
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PMID:Enforced and prolonged CD40 ligand expression triggers autoantibody production in vivo. 1174 68

CD40-CD40 ligand (CD40L) interactions play a critical role in the activationof cellular immunity. CD40L enhances the antigen presentation function of CD40-expressing B cells. We have used a murine B-cell lymphoma model (A20) to study the in vivo antitumor effect of the administration of tumor cells transduced with a recombinant adenovirus encoding CD40L (AdvCD40L). After infection with AdvCD40L, A20 tumor cells up-regulate several T-cell costimulatory molecules (CD80, CD86, ICAM-1, and LFA-3) and Fas expression. Animals vaccinated with irradiated tumor cells transduced with AdvCD40L are protected against a lethal dose of parental A20 tumor cells. Animals with pre-existing tumors treated with AdvCD40L-transduced tumor cells display inhibition of the tumor growth, and this treatment confers a survival advantage. In vivo depletion studies demonstrate that both CD4(+) and CD8(+) T cells mediate the antitumor immunity provided by AdvCD40L-transduced tumor cells. These results show that genetic modification of tumor B cells with CD40L can be a useful strategy to promote systemic immunity against B-cell malignancies and provide an in vivo system to allow for additional evaluation and refinement of this approach.
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PMID:In vivo antitumor effect of CD40L-transduced tumor cells as a vaccine for B-cell lymphoma. 1203 33

Transgenic mice overexpressing in B lymphocytes either Bcl-2 or a TNF receptor-associated factor (TRAF)2 mutant lacking the N-terminal RING and zinc finger domains located at the N terminus of the molecule (TRAF2DN), which mimics TRAF1, developed lymphadenopathy and splenomegaly due to polyclonal B cell expansion. Remarkably, TRAF2DN/Bcl-2 double-transgenic mice contained B cell populations similar to those observed in TRAF2DN mice. However, over time, they developed severe splenomegaly and lymphadenopathy, and most animals also developed leukemia, pleural effusion, and, in some cases, ascites associated with monoclonal and oligoclonal B cell neoplasms. The life span of TRAF2DN/Bcl-2 mice was markedly reduced compared with Bcl-2 and TRAF2DN single-transgenics or wild-type littermates. The expanded B cell population of TRAF2DN/Bcl-2 double-transgenic mice was primarily comprised of small/medium-size noncycling B220(M)/IgM(H)/IgD(L)/CD21(L)/CD23(NULL)/CD11b(+)/CD5+ cells that were Bcl-6-negative, consistent with a B-1 phenotype. The cells also expressed high levels of CD54 and other adhesion molecules. In vitro, these B cells showed comparable proliferation rates to those of wild-type counterparts but exhibited markedly increased survival and were resistant to apoptosis induced by chemotherapeutic agents and glucocorticoids. Histopathologic features were consistent with mouse small B cell lymphoma progressing to leukemia with many similarities to human chronic lymphocytic leukemia. Given that many human chronic lymphocytic leukemias overexpress TRAF1 and Bcl-2, our findings suggest that cooperation between Bcl-2 and TRAF pathways contributes to the development of this type of leukemia.
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PMID:TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice. 1554 99

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.
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PMID:Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab. 1655 Jul 55

We evaluated the expression of 10 adhesion molecules on peripheral blood tumor cells of 17 patients with chronic lymphocytic leukemia, 17 with mantle-cell lymphoma, and 13 with nodal or splenic marginal B-cell lymphoma, all in the leukemic phase and before the beginning of any therapy. The diagnosis of B-cell non-Hodgkin's lymphomas was based on cytological, histological, immunophenotypic, and molecular biology methods. The mean fluorescence intensity of the adhesion molecules in tumor cells was measured by flow cytometry of CD19-positive cells and differed amongst the types of lymphomas. Comparison of chronic lymphocytic leukemia and mantle-cell lymphoma showed that the former presented a higher expression of CD11c and CD49c, and a lower expression of CD11b and CD49d adhesion molecules. Comparison of chronic lymphocytic leukemia and marginal B-cell lymphoma showed that the former presented a higher expression of CD49c and a lower expression of CD11a, CD11b, CD18, CD49d, CD29, and CD54. Finally, comparison of mantle-cell lymphoma and marginal B-cell lymphoma showed that marginal B-cell lymphoma had a higher expression of CD11a, CD11c, CD18, CD29, and CD54. Thus, the CD49c/CD49d pair consistently demonstrated a distinct pattern of expression in chronic lymphocytic leukemia compared with mantle-cell lymphoma and marginal B-cell lymphoma, which could be helpful for the differential diagnosis. Moreover, the distinct profiles of adhesion molecules in these diseases may be responsible for their different capacities to invade the blood stream.
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PMID:Adhesion molecule profiles of B-cell non-Hodgkin's lymphomas in the leukemic phase. 1705 42

In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.
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PMID:Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma. 1841 22

We previously reported that the prognosis of CD21-positive diffuse large B-cell lymphoma (DLBCL) is significantly favorable to that of CD21-negative DLBCL (Otsuka et al. in Br J Haematol 127:416-424, 2004). In this study, we attempted to clarify the biological significance of CD21 expression in B-cell lymphoma (BCL) by performing in vitro experiments using CD21 transfection into a CD21-negative lymphoma cell line and analyzing clinical data from lymphoma samples. Established clones of CD21 transfectants showed homotypic aggregation in suspension culture. Analysis of integrin expression revealed that LFA-1 appeared to be expressed on CD21 transfectants, and the cell aggregation was abrogated by anti-LFA-1 antibody. The CD21 transfectants could adhere to plastic plates coated with ICAM-1. Moreover, flow cytometry and/or immunohistochemical analyses of clinical BCL samples (n = 29) revealed positive for CD21 in all cases; LFA-1 was also expressed without exception. All BCL cells isolated from cavity fluids (n = 10) failed to express both CD21 and LFA-1. These data suggest that CD21 is tightly related to LFA-1 expression in BCL and the absence of CD21/LFA-1 expression is associated with pleural/peritoneal fluid involvement by BCL, a potential indicator of disease progression of BCL.
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PMID:Clinical significance of co-expression of CD21 and LFA-1 in B-cell lymphoma. 1936 Apr 56

Fusion of dendritic cells and tumor cells (FCs) constitutes a promising tool for generating an antitumor response because of their capacity to present tumor antigens and provide appropriate costimulatory signals. CD40-CD40L interaction has an important role in the maturation and survival of dendritic cells and provides critical help for T-cell priming. In this study, we sought to improve the effectiveness of FC vaccines in a murine model of B-cell lymphoma by engineering FCs to express CD40L by means of an adenovirus encoding CD40L (Adv-CD40L). Before transduction with Adv-CD40L, no CD40L expression was detected in FCs, DCs or tumor cells. The surface expression of CD40L in FC transduced with Adv-CD40L (FC-CD40L) ranged between 50 and 60%. FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction. Furthermore, FC-CD40L showed enhanced migration to secondary lymphoid organs. Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-gamma, compared with controls. Treatment with the FC-CD40L vaccine induced regression of established tumors and increased survival. Our data demonstrate that FC transduced with Adv-CD40L enhances the antitumor effect of FC vaccines in a murine lymphoma model and this is associated with an increased Th17-type immune response.
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PMID:Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response. 2001 Jun 27

Rapid and accurate differential diagnosis between Burkitt lymphoma (BL) and CD10+ diffuse large B-cell lymphoma (DLBCL) is imperative because their treatment differs. Recent studies have characterized several antigens differentially expressed in these 2 types of lymphoma. Our goal was to determine whether use of these markers would aid in the differential diagnosis of BL vs CD10+ DLBCL by flow cytometric immunophenotyping (FCI). Twenty-three cases of CD10+ B-cell lymphomas with available cryopreserved samples were identified (13 BL and 10 CD10+ DLBCL). Multiparameter FCI was performed using the following antibodies: CD18, CD20, CD43, CD44, and CD54 and isotype controls. Expression of CD44 and CD54 was detected at a significantly lower level in BL compared with CD10+ DLBCL (P = .001 and P = .01, respectively). There was not a significant difference in expression of CD18 and CD43. Our data show that expression of CD44 and CD54 differs significantly between BL and CD10+ DLBCL.
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PMID:A novel flow cytometric antibody panel for distinguishing Burkitt lymphoma from CD10+ diffuse large B-cell lymphoma. 2039 18

CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.
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PMID:Human CD14hi monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression. 2212 10


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