Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously described the existence of a tonsillar IgD- B cell subset with memory B cell features. To test the possibility that these cells could derive from germinal center (GC) B cell precursors, we examined the proliferation, differentiation, and phenotype of GC B cells after culturing with either anti-CD40 Abs or activated T cells, presumably mimicking the signals received by centrocytes in the light zone of GC. We show in this work that GC B cells proliferate and secrete Igs in both activation systems, thus indicating that CD40 ligation is also required for differentiation of GC B cells along the plasmacytoid pathway. T cell-dependent activation of GC B cells induced down-regulation of most GC-related markers (CD10, CD38, and CD77) and up-regulation of CD44 and CD62-L which are both expressed on the putative memory B cells subset. Moreover, T cell-mediated stimulation of GC B cells resulted in the strong induction of CD5 and up-regulation of APO-1/Fas (CD95). In contrast, stimulation performed with immobilized anti-CD40 Abs did not affect expression of CD10 and CD38 and failed to induce CD62-L and CD5, suggesting that the CD40 signaling pathway is necessary but not sufficient for the development of memory B cells. CD95 ligation on GC B cells was found to antagonize the stimulatory effect of immobilized anti-CD40 Abs on their proliferation, survival, and Bcl-2 expression. The possible role of CD95 in the expansion and selection of the Ag-activated B cell clones in GC is discussed.
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PMID:Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule. 753 29

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.
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PMID:Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. 855 Dec 26

Follicular lymphomas are thought to arise from the follicle center B cells and are characterized by follicular structures that recapitulate many features of normal secondary lymphoid follicles. The neoplastic B cells of follicular lymphoma reside not only in follicles but also in the interfollicular zone in which they form a diffuse infiltrate. We have investigated the frequency, extent, and biological characteristics of this interfollicular component in 30 cases of follicular lymphoma. An interfollicular B-cell infiltrate of variable extent (minimal, moderate, or prominent) was present in all cases. Morphologically interfollicular neoplastic B cells were small centrocyte-like cells with lower grade cytology and lower proliferation fraction compared with the neoplastic follicles. The neoplastic phenotype of these cells (CD20+, light chain restricted) was confirmed in 18 cases. Clonal identity between the follicular and interfollicular components was shown in five cases using microdissection and PCR amplification of immunoglobulin heavy chain genes. Analysis of Ig heavy chain gene sequences showed identical variants of tumor subclones in both follicular and interfollicular compartments, indicating active tumor cell traffic between the two. In six cases in which frozen tissue was available, the immunophenotype of follicular and interfollicular tumor cells were compared using immunohistochemistry. Activation markers such as CD10, CD38, and CD95 and T-cell costimulatory molecules CD80 and CD86, which were expressed by neoplastic follicles, were either downregulated or absent in the interfollicular component in most of the cases. The low-grade cytological features, low proliferation fraction, and downregulation of activation markers in the interfollicular neoplastic B cells suggests that these are resting cells analogous to memory B cells of normal lymphoid tissues. The presence of such a resting tumor cell subpopulation in the majority of follicular lymphomas may partly account for the remarkable resistance to therapy of this disease.
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PMID:Follicular lymphomas contain a clonally linked but phenotypically distinct neoplastic B-cell population in the interfollicular zone. 961 69

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.
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PMID:CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients. 988 5

The precise signaling pathways to induce a germinal center (GC) phenotype and somatic mutations in human B cells are presently not understood. Major phenotypical hallmarks of a human GC B cell are up-regulated expression of CD10 and CD95 together with a heterogeneous expression of CD77. Activation of resting human tonsillar B cells using anti-CD40 and anti-IgM antibodies normally only induces up-regulation of CD38 and CD71 but has no effect on the typical GC markers. However, we show here that an additional co-ligation of the glycoprotein CD44 on such tonsillar B cells up-regulated the typical human GC markers CD10, CD38, CD77 and CD95, and down-regulated CD24 and CD39 as well as induced progression towards apoptosis in these cells; all characteristics of GC B cells. These data indicate a functional role of CD44 during activation of human naive B lymphocytes and in the generation of GC B cells.
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PMID:Co-ligation of CD44 on naive human tonsillar B cells induces progression towards a germinal center phenotype. 1033 Feb 79

We analyzed CD95(Fas/APO-1) antigen expression on bone marrow blasts in 38 children with acute lymphoblastic leukemia (ALL) receiving a treatment in the Department of Leukaemias at the Cancer Research Center in 1987-1989 years (n = 22) and in 1994-1997 years (n = 16). CD95 antigen expression was studied by monoclonal antibodies (MoAbs) IPO-4 in indirect immunofluorescence analysis. CD95 antigen was expressed on 35.8 +/- 7.5% bone marrow blasts, most frequently (63.6%) in the clinically favourable Pre-B ALL. Only in this group CD95 antigen expression was correlated with CD10 antigen expression that has a positive influence to the time of complete remission in ALL patients. Our data showed that CD95 expression on blast cells is a favourable prognostic sign, associated with increased relapse-free and total survival. On the contrary, the absence of CD95 antigen on blasts is an unfavourable sign for disease evolution.
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PMID:CD95 (FAS/APO-1) antigen is a new prognostic marker of blast cells of acute lymphoblastic leukaemia patients. 1050 Aug

This study shows that human postthymic T cells express CD10 when undergoing apoptosis, irrespective of the signal responsible for initiating the apoptotic process. Cells from continuous T-cell lines did not normally express CD10, but became CD10(+) when induced into apoptosis by human immunodeficiency virus (HIV) infection and exposure to CD95 monoclonal antibody, etoposide, or staurosporin. Inhibitors of caspases blocked apoptosis and CD10 expression. Both CD4(+) and CD8(+) T cells purified from normal peripheral blood expressed CD10 on apoptotic induction. CD10 was newly synthesized by the apoptosing cells because its expression was inhibited by exposure to cycloheximide and CD10 mRNA became detectable by reverse transcription-polymerase chain reaction in T cells cultured under conditions favoring apoptosis. To show CD10 on T cells apoptosing in vivo, lymph node and peripheral blood T cells from HIV(+) subjects were used. These suspensions were composed of a substantial, although variable, proportion of apoptosing T cells that consistently expressed CD10. In contrast, CD10(+) as well as spontaneously apoptosing T cells were virtually absent in peripheral blood from normal individuals. Collectively, these observations indicate that CD10 may represent a reliable marker for identifying and isolating apoptosing T cells in vitro and ex vivo and possibly suggest novel functions for surface CD10 in the apoptotic process of lymphoid cells.
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PMID:Expression of CD10 by human T cells that undergo apoptosis both in vitro and in vivo. 1055 91

Negative selection is a process by which autoreactive lymphocytes are eliminated from the developing antigen receptor repertoire. The mechanisms regulating negative selection of immature B lymphocytes in the bone marrow are poorly elucidated. Human bone marrow cells were examined in order to investigate the presence of the members of the Fas (APO-1/CD95) system. Here we demonstrate the expression of Fas in immature B lymphocytes (CD10/CD19+/CD40+/sIg+), and the presence of Fas natural ligand (FasL) in CD19+ bone marrow cells. The observed expression of apoptosis-related molecules might indicate how negative selection of autoreactive B cells can occur in human bone marrow.
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PMID:Immature B cells in bone marrow express Fas/FasL. 1073 97

Primary mediastinal B-cell lymphoma is a locally highly aggressive but poorly disseminating tumor composed of medium sized or large cells most probably of thymic medullary origin. It has a mature B-cell phenotype, typically lacks immunoglobulin expression and has variable defects in expression of HLA-molecules. We present here a cell line, MedB-1, derived from such a tumor. As is frequently found in mediastinal B-cell lymphomas in situ, MedB-1 is CD10(-), CD19(+), CD21(-), CD22(+), CD23(+), CD25(-), CD37(+), CD38(-), CD39(+), CD40(+), CD54(+), CD95(+). Like the parental tumor, MedB-1 lacks HLA-A,B,C alpha-chains and beta(2)microglobulin and expresses HLA-D molecules at decreased levels. Both parental tumor and MedB-1 cells are clonally related as shown by immunoglobulin heavy chain gene rearrangement analysis. Unlike the parental tumor tissue, the MedB-1 cell line cytoplasmically expresses IgG/kappa in a very small subset of cells under standard culture conditions. MedB-1 does not contain any Epstein-Barr virus DNA. In a tissue adhesion assay MedB-1 cells showed an extensive binding to the medullary region of normal thymus. Altogether, MedB-1 is a suitable tool for functional and molecular analysis of this distinct lymphoma entity.
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PMID:MedB-1, a human tumor cell line derived from a primary mediastinal large B-cell lymphoma. 1129 Oct 70

B lymphocytes that infiltrate the thyroid (Thy-B cells) in Graves' patients appear to be implicated in the pathophysiology of this disorder. The goal of the present study was to examine the nature of these Thy-B cells. To this end, Thy-B lymphocytes were isolated from surgical thyroidal samples, and their phenotype was determined by using mouse monoclonal antibodies (mAb) directed against a wide variety of surface markers, followed by flow cytometry multicolor analysis. The results show that most Thy-B cells (approximately 60%) exhibited IgM(+) IgD(low to -) surface immunoglobulin (Ig) profile, whereas the minor cell fraction (approximately 30%) consisted of switched IgG(+) memory B lymphocytes. Thy-B cells expressed low levels of CD5, CD23, and CD62L, which distinguished them from the resting B-cell pool, the major B-cell subset in the blood. In addition, they lacked CD38, CD10, and CD71, characteristic molecules for the germinal center B lymphocytes. In addition, Thy-B lymphocytes showed peculiar patterns both of adhesion molecules (CD62L(-), CD44(intermediate)), and of activation molecules (CD69(+), CD80(+), and, in part, CD95(+)). Taken together, these results suggest that the Thy-B lymphocyte subset consists of a combination of IgM(+) B cells resembling marginal zone B lymphocytes, and isotype-switched memory B cells.
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PMID:Thyroid-infiltrating B lymphocytes in Graves' disease are related to marginal zone and memory B cell compartments. 1144 98


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