scholarly journals Interferon-alpha induces the expression of the L-selectin homing receptor in human B lymphoid cells.

1993 ◽  
Vol 123 (6) ◽  
pp. 1889-1898 ◽  
Author(s):  
S S Evans ◽  
R P Collea ◽  
M M Appenheimer ◽  
S O Gollnick
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Cell Line ◽  
Surface Density ◽  
Surface Expression ◽  
Lymphoid Cells ◽  
Homing Receptor ◽  
Ifn Alpha ◽  
Peripheral Lymph ◽  
B Lymphoid

The L-selectin homing receptor expressed by lymphocytes mediates the initial attachment of these cells to high endothelial venules within peripheral lymph nodes. This adhesive interaction is required for the migration of B and T lymphocytes from the blood into peripheral lymph nodes. There is currently little information regarding the nature of the factors involved in the regulation of the synthesis and expression of L-selectin by lymphocytes. In this report, the immunomodulatory cytokine interferon-alpha (IFN-alpha) was shown to markedly upregulate the surface density of L-selectin in the established human B lymphoid Daudi cell line and in a subpopulation of tissue-derived human B lymphoid cells. Other cytokines such as IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and low molecular weight B cell growth factor did not affect L-selectin surface expression in the model Daudi B cell line. Upregulation of L-selectin surface density in IFN-alpha-treated Daudi B cells correlated directly with an increase in L-selectin mRNA steady state levels and enhanced L-selectin-dependent binding to a carbohydrate-based ligand, phosphomonoester core polysaccharide. Regulation of L-selectin mRNA by IFN-alpha had characteristics similar to that of classical IFN-stimulated genes including rapid kinetics of induction, protein-synthesis-independent induction, and sensitivity to tyrosine-kinase inhibitors. IFN-alpha did not upregulate L-selectin mRNA levels or surface expression in an IFN-resistant Daudi subclone which exhibits a defect in the signal transduction pathway required for the transcriptional induction of IFN-stimulated genes. These data demonstrate a fundamental role for IFN-alpha in regulating L-selectin synthesis and expression in human B lymphoid cells and suggest a mechanism whereby this cytokine regulates the regional trafficking of B cells to peripheral lymph nodes.

VCAM-1 Expression in B-Lymphopoiesis and Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3247-3247
Author(s):  
Faith M. Young ◽  
Raymond E. Felgar ◽  
Antonia P. Eyssallenne ◽  
Andrea Bottaro ◽  
Timothy P. Bushnell
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Stromal Cell ◽  
Ex Vivo ◽  
Surface Expression ◽  
Lymphoid Cells ◽  
B Lymphoid

Abstract Vascular Cell Adhesion Molecule-1 (VCAM; CD106), a member of the Ig Superfamily of molecules, binds to the β-1 integrin, Very Late Antigen-4 (VLA-4; CD49d); this interaction plays an integral role in leukocyte trafficking as well as lymphocyte-stromal cell interactions. VCAM can be shed from the surface of cells, and, in humans, serum levels of soluble VCAM (sVCAM) parallel activity and remission states in acute lymphocytic leukemia (ALL) and inflammation. Although widely investigated as a stromal-cell associated molecule, our lab and others have recently identified VCAM expression on normal bone-marrow derived B-lymphoid cells. Using FACS technology, we found that surface expression of VCAM is closely modulated at specific stages of B cell development, with relatively high levels on the pro-B cell population, down-modulation in pre-B cells at the onset of immunoglobulin (Ig) gene rearrangement, and subsequent re-expression at variable levels in immature and mature peripheral B cell subsets. We have verified VCAM transcripts by cDNA PCR in highly purified populations of murine precursor B cells. Normal human bone marrow precursor B-lymphoid populations (hematogones) also demonstrate VCAM surface protein expression. Finally, in an animal model of BCR/ABL+ ALL, we found that VCAM expression is dramatically increased on lymphoblasts when compared to normal reference populations in bone marrow and spleen. VCAM expression in human lymphoid malignancies is currently under investigation. Antibody-mediated VCAM cross-linking on primary B-cell precursors ex-vivo generates intracellular reactive oxygen species, demonstrating that signaling through this molecule has functional consequences. Intriguingly, in-vivo, VCAM expression is limited to B-lymphoid cells harvested from tissues such as bone marrow, spleen and lymph node; since, in the same animal, peripheral blood lymphocytes and peritoneal cells do not express readily detectable levels of the surface antigen. VCAM-expressing B-lymphoid cells cultured ex-vivo gradually lose surface expression over 24 hours. The tissue-associated modulation of VCAM expression is preserved in the murine Ph+ lymphoblasts; leukemia cells isolated from the peripheral blood express very low levels of surface VCAM compared to those harvested from bone marrow or spleen. Our data suggests that VCAM expression is dependent on tissue-specific microenvironmental signals in-vivo. B-lymphoid expression of both VCAM and its ligand VLA-4 is a surprising finding that has broad implications regarding leukemic cell interaction with endothelial cells, the bone marrow retention and trafficking of precursor- and leukemic-B cell populations, and the interpretation of an extensive experimental database predicated on the stromal-cell specificity of VCAM expression and function.

scholarly journals Primary Diffuse Large B-cell Lymphoma involving the Mandible

2015 ◽  
Vol 16 (10) ◽  
pp. 840-844 ◽  
Author(s):  
Zeeshan H Ahmad ◽  
Sukumaran Anil ◽  
Abdulsalam S Aljabab ◽  
Ibraheem HM Motabi ◽  
Abdullah Alrashed
Keyword(s):  
B Cell ◽  
Clinical Presentation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Large B Cell Lymphoma ◽  
Rare Malignancy ◽  
B Lymphoid ◽  
Immunologic Profile ◽  
Large B Cell

ABSTRACT Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma histologically characterized by diffuse proliferation of large neoplastic B-lymphoid cells with a nuclear size equal to or exceeding normal histiocytic nuclei. A case of DLBCL of the mandible in an 18 years old male patient is presented. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment and prognosis. Though lymphoma of mandible is rare, it must be considered in differential diagnosis of swellings arising in the region. How to cite this article Alshahrani FAA, Aljabab AS, Motabi IHM, Alrashed A, Anil S. Primary Diffuse Large B-cell Lymphoma involving the Mandible. J Contemp Dent Pract 2015;16(10):840-844.

Core 2 branching β1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4104-4112 ◽  
Author(s):  
Jean-Marc Gauguet ◽  
Steven D. Rosen ◽  
Jamey D. Marth ◽  
Ulrich H. von Andrian
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Rolling Velocity ◽  
Peripheral Lymph

Abstract Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)

Hemophagocytic Syndrome in a Case of Splenic Large B-Cell Lymphoma

1996 ◽  
Vol 82 (6) ◽  
pp. 621-624 ◽  
Author(s):  
Gualtiero Büchi ◽  
Giuseppe Termine ◽  
Renzo Orlassino ◽  
Mauro Pagliarino ◽  
Roberto Boero ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
B Cell ◽  
Diagnostic Criteria ◽  
Hemophagocytic Syndrome ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Peripheral Lymph ◽  
Large B Cell

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.

scholarly journals Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation

Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4898-4906 ◽  
Author(s):  
Andrea Hoelbl ◽  
Boris Kovacic ◽  
Marc A. Kerenyi ◽  
Olivia Simma ◽  
Wolfgang Warsch ◽  
...  
Keyword(s):  
B Cell ◽  
Fetal Liver ◽  
Transgenic Animals ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
In Vitro Assays ◽  
Cell Stage ◽  
Lymphoid Development ◽  
B Lymphoid

AbstractThe Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/bΔN/ΔN mice). We have now reanalyzed lymphoid development in Stat5a/bnull/null mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/bnull/null mice lacked CD8+ T lymphocytes. A massive reduction of CD8+ T cells was also found in Stat5a/bfl/fllck-cre transgenic animals. While γδ T-cell receptor–positive (γδTCR+) cells were expressed at normal levels in Stat5a/bΔN/ΔN mice, they were completely absent in Stat5a/bnull/null animals. Moreover, B-cell maturation was abrogated at the pre–pro-B-cell stage in Stat5a/bnull/null mice, whereas Stat5a/bΔN/ΔN B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/bnull/null cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/bΔN/ΔN-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/bΔN/ΔN and Stat5a/bnull/null mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation.

Aberrant Expression of Golgin-84 in Non-Hodgkin Lymphomas and Plasma Cell Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4633-4633
Author(s):  
Ling Chen ◽  
Yaling Yang ◽  
C. Cameron Yin ◽  
Gary Lu ◽  
Su Chen ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Plasma Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Plasma Cell Myeloma ◽  
Expression Levels ◽  
Non Hodgkin Lymphoma

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

Leukemic-Phase Diffuse Large B-Cell Lymphoma with t(14;18), CDKN2A and MLL Deletion Presenting with an Infiltrative Skin Rash

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5419-5419
Author(s):  
Iris Y Sheng ◽  
Diana Olguta Treaba ◽  
Kenneth D. Bishop
Keyword(s):  
Emergency Department ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Medial Malleolus ◽  
Large B Cell Lymphoma ◽  
Leukemic Phase ◽  
B Lymphoid ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a curable, highly aggressive subtype of non-Hodgkin's lymphoma (NHL). It typically manifests as a rapidly-growing mass in a lymph node or extranodal distribution. Outcomes in this disease have improved significantly with the incorporation of anti-CD20 monoclonal antibodies in addition to combination chemotherapy. Further characterization of molecular and pathologic subtypes of DLBCL is currently the subject of intensive investigation, and optimal therapy for specific subtypes of DLBCL remains to be determined. We report the case of a 66-year-old woman who presented to the Emergency Department with a diffuse, non-pruritic, purple rash of her bilateral lower extremities of one week duration. The rash was accompanied by one episode of subjective fever and lower back pain. The patient did not endorse night sweats or weight loss prior to presentation. Physical examination revealed a healthy-appearing woman with systemic pallor, non-blanching, pink/purple papules over both lower extremities, and one indurated, pink/brown, firm plaque over the left medial malleolus (Image 1-3). Laboratory studies revealed a leukocytosis with a total white blood cell count of 46.6x109/L (28% polymorphonuclear cells, 13% band forms, 16% lymphocytes, and 34% atypical lymphoid cells), lactate dehydrogenase >3600 IU/L, uric acid 15.2 mg/dL. Radiographic studies of the chest, abdomen, and pelvis revealed only minimally-prominent mesenteric lymph nodes, which were not reported as pathologically enlarged, with no other mass or potential primary lesion identified. Flow cytometry of peripheral blood identified 44% neoplastic B-lymphoid cells expressing CD19, CD20, CD10, and CD38. The hypercellular bone marrow had 80-90% blast-like, surface IgG positive B-lymphoid cells, positive for MUM1, CD10 and bcl2 and in a small subset (10%) positive for c-myc. They were cyclin D1, CD34 and TdT negative. FISH studies detected the presence of t(14;18), IGH-BCL2 fusion, and deletion of both CDKN2A and MLL; a c-myc rearrangement was not detected. A punch biopsy of the right medial malleolus showed dense infiltration of the subcutaneous fat and dermis by CD20, CD10, MUM-1, CD31positive B- lymphoid cells in a subset also bcl6 positive. Together, these findings were interpreted to be most consistent with a leukemic-phase DLBCL. Given previous reports that DLBCL with CDKN2A deletions have poor outcomes with standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)1, treatment was initiated with dose-adjusted rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone (DA-R-EPOCH). The patient subsequently transferred care to another institution and continued treatment with R-CHOP and methotrexate (MTX). The patient's rash and leukocytosis resolved after the first cycle of DA-R-EPOCH. After the third cycle of R-CHOP and MTX, the patient presented to the Emergency Department with febrile neutropenia and mucositis, and was found to have a methotrexate level of 0.19 µMol/L. She ultimately died due to complications from severe sepsis. In summary, we present a patient with a rare presentation of leukemic-phase DLBCL, with the first reported case of skin infiltration from this entity. Further studies are necessary to determine treatment with optimal outcomes and minimal toxicity for this and other rare subtypes of DLBCL. Reference: 1. Jardin, F., et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 116(7): 1092-1104. 2010 Figure 1 Left ankle Figure 1. Left ankle Figure 2 Right Calf Figure 2. Right Calf Figure 3 Right leg Figure 3. Right leg Disclosures No relevant conflicts of interest to declare.

JunB inhibits proliferation and transformation in B-lymphoid cells

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4159-4165 ◽  
Author(s):  
Agnieszka P. Szremska ◽  
Lukas Kenner ◽  
Eva Weisz ◽  
Rene G. Ott ◽  
Emmanuelle Passegué ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Transgenic Animals ◽  
Inhibitory Effect ◽  
Lymphoid Cells ◽  
Negative Regulator ◽  
Transgenic Cells ◽  
B Lymphoid

Abstract The activator protein 1 (AP-1) member JunB has recently been implicated in leukemogenesis. Here we surveyed human lymphoma samples for expression of JunB and other AP-1 members (c-Jun, c-Fos, Fra1, JunD). JunB was strongly expressed in T-cell lymphomas, but non-Hodgkin B-cell lymphomas do not or only weakly express JunB. We therefore asked whether JunB acted as a negative regulator of B-cell development, proliferation, and transformation. We used transgenic mice that expressed JunB under the control of the ubiquitin C promoter; these displayed increased JunB levels in both B- and T-lymphoid cells. JunB transgenic cells of B-lymphoid, but not of T-lymphoid, origin responded poorly to mitogenic stimuli. Furthermore, JunB transgenic cells were found to be less susceptible to the transforming potential of the Abelson oncogene in vitro. In addition, overexpression of JunB partially protected transgenic mice against the oncogenic challenge in vivo. However, transformed B cells eventually escaped from the inhibitory effect of JunB: the proliferative response was similar in explanted tumor-derived cells from transgenic animals and those from wild-type controls. Our results identify JunB as a novel regulator of B-cell proliferation and transformation. (Blood. 2003;102:4159-4165)

The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP

1992 ◽  
Vol 12 (6) ◽  
pp. 2662-2672
Author(s):  
Z Kozmik ◽  
S Wang ◽  
P Dörfler ◽  
B Adams ◽  
M Busslinger
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
B Cell ◽  
Lymphoid Cells ◽  
Binding Studies ◽  
Specific Transcription Factor ◽  
High Affinity ◽  
B Lymphoid

The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.

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