Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV-1), induces a chronic expansion of the B lymphocyte population (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) and control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.
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PMID:Bovine leukaemia virus-induced lymphocytosis in sheep is associated with reduction of spontaneous B cell apoptosis. 901 Feb 99

Small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) are small B-cell lymphomas that share many morphological and immunophenotypic features, both expressing the T-cell antigen CD5. Because of this, there is speculation that these two lymphomas may have a common origin, both arising from the mantle zone of the lymph node. CD44 (HCAM), a glycoprotein "homing receptor," has been reported as a marker of small B-cell lymphomas for determining behavior as well as the nodal cell of origin. Intensity of CD44 expression also has been correlated with dissemination of lymphoma. We studied 50 cases with classic features of SLL (30 cases) or MCL (20 cases). Immunophenotypic analysis was performed on paraffin sections. All cases of MCL and SLL were CD20 positive; CD5 was expressed in 19 of 25 (76%) SLL and 11 of 15 (73%) MCL. Cyclin D1 was expressed in 11 of 17 (76%) MCL and no cases of SLL. CD43 coexpression was seen in 27 of 29 (93%) SLL and 17 of 19 (89%) MCL. CD23 was positive in 25 of 28 (89%) SLL and 2 of 20 (10%) MCL. Bcl-2 was positive in 18 of 22 (82%) SLL and 15 of 16 (94%) MCL. CD44 was positive with moderate to strong intensity in 11 of 30 SLL and 15 of 20 MCL. Peripheral blood involvement did not correlate with CD44 immunoreactivity. MCL tended to have intense CD44 immunoreactivity, whereas SLL tended to show weaker CD44 intensity. This trend in the intensity of CD44 in MCL suggests that CD44 may be helpful in distinguishing SLL from MCL and possibly elucidating the origin of these CD5-positive B-cell neoplasms.
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PMID:Expression of CD44 (HCAM) in small lymphocytic and mantle cell lymphoma. 978 54

To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras-RAG). Similar to the effects of an immunoglobulin (Ig) mu heavy chain (HC) transgene, activated Ras caused progression of RAG1-deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of lambda5, RAG2, and germline kappa locus transcripts. However, these Ras-RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig mu HC together with a Bcl-2 transgene. Taken together, these findings suggest that activated Ras signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals.
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PMID:Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes. 987 69

B lymphocyte production in murine bone marrow is negatively regulated by sex steroids and the aim of this study was to identify early hormone sensitive checkpoints. Estrogen (E2) treatment reduced cmu(+) pre-B cells, a change that occurred concomitantly with decreased Ig gene rearrangements and rag-1 transcripts. Estrogen decreased B lineage precursors in Ig transgenic mice, demonstrating that hormonal regulation is independent of the recombination process. B lineage precursors in Bcl-2 transgenic mice were resistant to estrogen treatment, suggesting that life/death decisions are involved in hormonal regulation. A previously uncharacterized population of CD43(-)cmu(-) B lineage precursors was identified in normal, Ig transgenic, and RAG(-/-) mice after estrogen treatment, revealing that down-regulation of CD43 can occur independent of Ig heavy chain expression. These cells expressed transcripts for both tdt and bcl-2, characteristics of early B-cell precursors. BrdU incorporation analysis revealed that the mitotic activity of early B-lineage cells is reduced in hormone-treated mice. We conclude that sex steroids modulate the production of B-lineage cells by influencing the differentiation, proliferation, and survival of early B-cell precursors. These findings are informative about mechanisms of hormonal regulation, as well as the significance of some differentiation-related events. (Blood. 2000;95:2059-2067)
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PMID:Estrogen influences the differentiation, proliferation, and survival of early B-lineage precursors. 1070 75

Primary cutaneous B-cell lymphomas (PCBLs) may have particular clinicopathologic characteristics distinct from their lymph node-based counterparts. It has been suggested that PCBLs should have a separate classification system. The aim of this study was to determine whether the Revised European-American Lymphoid Neoplasms (REAL) classification is applicable to PCBL. Thirty-nine cases of PCBL from 36 patients, consisting of 20 men and 16 women (median age 66 yrs), were included in this study. Paraffin-section immunohistochemistry for CD3, CD5, CD10, CD20, CD43, Bcl-2, Bcl-6, and cyclin D1 was performed in all cases. Immunostaining for immunoglobulin light chains was also performed on cases histologically diagnosed as extranodal marginal zone lymphoma (MZL) and primary cutaneous B-cell lymphoma unclassifiable (PCBLu). Polymerase chain reaction (PCR) analysis of t(14;18) was performed in all cases. Immunoglobulin heavy chain gene rearrangement (VDJ) was tested by PCR on all follicle center lymphoma (FCL), MZL, and PCBLu cases. The 39 cases consisted of 15 (39%) FCLs, 13 (33%) diffuse large B-cell lymphomas (DLCL), 9 (23%) extranodal MZL, and 2 cases of PCBLu. Anatomically, 59% of PCBLs occurred in the head and neck, of which approximately 57% were FCL. Five of six cases presenting on the lower extremity were DLCL. Follow-up data was available from all 39 patients with a mean of 50.8 months. All but two patients are alive with or without disease at last contact. One patient with DLCL died of lung metastases and the other DLCL patient died of sepsis as a complication of therapy. In all 15 cases of FCL, CD10 and/or Bcl-6 expression supported the follicle center origin of the neoplastic cells. In contrast to previous reports, we found that 53% (8 of 15) of primary cutaneous FCL had either Bcl-2 protein expression or t(14;18). Our data indicate that many cases of primary cutaneous FCL have Bcl-2 alterations similar to their nodal counterpart. We found that 95% (37 of 39) of PCBLs could be classified according to the REAL classification, supporting its applicability in cutaneous lymphomas.
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PMID:Clinicopathologic reassessment of primary cutaneous B-cell lymphomas with immunophenotypic and molecular genetic characterization. 1125 30

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the J(H) gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.
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PMID:Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma. 1245 11

Cutaneous follicle center lymphoma (FCL) is reported to have a unique immunophenotype and clinical course as compared with nodal FCL. We studied 19 cases of FCL of the skin using paraffin embedded tissue. An immunohistochemistry panel included CD45, CD3, CD20, CD43, CD21, bcl-2, bcl-6, CD5, and CD10. Molecular studies were performed by polymerase chain reaction for immunoglobulin heavy chain (IgH) and t(14;18). Trisomy 3 was performed by fluorescent in situ hybridization (FISH) in 13 cases. Follow up was obtained in 17 cases (range 3 to 137 months). Patients included 10 females and 9 males ranging in age from 33 to 88 years at first presentation (mean, 64). Twelve of 19 presented in the head and neck and 6 in the trunk and 1 on the arm. All had no known lymph node disease at presentation. Seventeen patients had no nodal disease with a minimum 3 month follow-up; 2/19 had unknown lymph node status with no follow-up. All cases were immunoreactive with CD20 and negative with CD3. Bcl-2 was immunoreactive in 11/18 cases, bcl-6 in 15/15, CD10 in 14/17, CD43 in 2/16 (both were CD10 immunoreactive) and CD5 in 1/15 (it was also bcl-6 immunoreactive). Eight of 18 cases were monoclonal for IgH. Three of 17 showed the presence of t(14;18). FISH was positive in 4 cases for trisomy 3 ranging from 16 to 22% (12% threshold). Follow-up showed no evidence of disease in 14/17 patients (4 to 137 mos). 3/17 patients are alive with disease (17 to 100 mo), and no patients died of disease.
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PMID:Cutaneous follicle center lymphoma: a clinicopathologic study of 19 cases. 1155 77

We have identified a novel subset of early B lineage cells in the mouse bone marrow (BM) by GL7 expression on cell surface. GL7(+)B220(low) BM cells have a large cell size and are CD43(-to low), CD95(-), Sca-1(-), I-A(low), IgM(-) and IgD(-), suggesting that they are large pre-B cells. These BM cells express lambda5 and VpreB but not terminal deoxytransferase (TdT) and Bcl-2, and approximately 50 % of them are in cell cycle. This fraction was not detected in BM cells of Rag-1-deficient and Scid mice, supporting that GL7(+)B220(low) BM cells belong to fraction C' and D according to Hardy's criteria or to an early large pre-B-II fraction according to Melchers-Rolink's criteria. Furthermore, GL7(+)B220(low) BM cells can differentiate into IgM(+) immature B cells in co-culture with stromal cells. These results suggest that B lymphocytes pass through the GL7(+) pre-B cell stage during differentiation in the BM. Thus, GL7 is the critical marker to define the proliferation stage of large pre-B cells.
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PMID:GL7 defines the cycling stage of pre-B cells in murine bone marrow. 1178 20

During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43(-/-) mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific CD8 T cell response in vivo but plays a more significant role in trafficking of CD8 T cells to tissues such as the brain. More interestingly, CD43 plays a role in the contraction of the immune response, with CD43(-/-) mice showing increased numbers of Ag-specific CD8 T cells following initial expansion. Following the peak of expansion, Ag-specific CD8 T cells from -/- mice show similar proliferation but demonstrate increased Bcl-2 levels and decreased apoptosis of Ag-specific effector CD8 T cells in vitro. Consistent with a delay in the down-modulation of the immune response, following chronic viral infection CD43(-/-) mice show increased morbidity. These data suggest a dynamic role of CD43 during an immune response: a positive regulatory role in costimulation and trafficking of T cells to the CNS and a negative regulatory role in the down-modulation of an immune response.
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PMID:Dynamic regulation of T cell immunity by CD43. 1205 10

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.
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PMID:Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion. 1207 68


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