scholarly journals Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70

Blood ◽  
2010 ◽  
Vol 115 (15) ◽  
pp. 3051-3057 ◽  
Author(s):  
Joanne Shaw ◽  
Yui-Hsi Wang ◽  
Tomoki Ito ◽  
Kazuhiko Arima ◽  
Yong-Jun Liu
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Cell Growth ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Memory B Cells ◽  
Receptor Ligand ◽  
Cell Growth And Differentiation ◽  
Necrosis Factor

Abstract The ability of plasmacytoid dendritic cells (pDCs) to promote plasma cell differentiation and immunoglobulin (Ig) secretion through the production of type I interferon and interleukin-6 has been well documented, although the role of additional factors, including tumor necrosis factor receptor-ligand interactions, has not been addressed. On stimulation with the Toll-like receptor ligand CpG (B type, 2006) we found that pDCs exhibit strong and stable expression of CD70, a tumor necrosis factor family ligand that binds to its receptor CD27 expressed on memory B cells and promotes plasma cell differentiation and Ig secretion. Using a pDC/B-cell coculture system, we found that CpG-stimulated pDCs can induce the proliferation of CD40L-activated human peripheral B cells and Ig secretion. This occurs independently of interferon and residual CpG, and requires physical contact between pDCs and B cells. CpG-stimulated pDCs can induce the proliferation of both naive and memory B cells, although Ig secretion is restricted to the memory subset. Blocking the interaction of CD70 with CD27 using an antagonist anti-CD70 antibody reduces the induction of B-cell proliferation and IgG secretion by CpG-stimulated pDCs. We have therefore identified CD70 as an important factor in the regulation of B-cell growth and differentiation by pDCs.

scholarly journals BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth

1999 ◽  
Vol 189 (11) ◽  
pp. 1747-1756 ◽  
Author(s):  
Pascal Schneider ◽  
Fabienne MacKay ◽  
Véronique Steiner ◽  
Kay Hofmann ◽  
Jean-Luc Bodmer ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Growth ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Immunoglobulin M ◽  
Biological Responses ◽  
Membrane Bound ◽  
And Function ◽  
Necrosis Factor

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M–stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center–like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

scholarly journals Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

2000 ◽  
Vol 192 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Jeffrey S. Thompson ◽  
Pascal Schneider ◽  
Susan L. Kalled ◽  
LiChun Wang ◽  
Eric A. Lefevre ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Cell Population ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-κB/Rel–regulated inhibitors of apoptosis

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3749-3756 ◽  
Author(s):  
Gerd Munzert ◽  
Dieter Kirchner ◽  
Heike Stobbe ◽  
Lothar Bergmann ◽  
Roland M. Schmid ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Lymphocytic Leukemia ◽  
Inhibitors Of Apoptosis ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a resistance toward apoptosis-inducing agents. Nuclear factor-κB (NF-κB)/Rel has been shown to regulate the expression of antiapoptotic genes, such as members of the inhibitor of apoptosis protein (IAP) and tumor necrosis factor receptor-associated factor (TRAF) gene families. Expression and regulation of NF-κB/Rel–dependent inhibitors of apoptosis have not been collectively studied in B-CLL. We examined expression of known NF-κB/Rel–regulated antiapoptotic genes by RNAse protection assay, real-time polymerase chain reaction, and immunoblotting in patients with B-CLL. TRAF1 and to a lesser extent TRAF2 were overexpressed in B-CLL lymphocytes as compared with normal CD19+ B cells. TRAF1 overexpression did not correlate with markers of disease progression or overall survival. Furthermore, we found high constitutive expression of the IAP genes c-IAP-1, c-IAP-2, and XIAP both in normal and B-CLL lymphocytes. Focusing on the regulation of TRAF1, NF-κB/Rel activity in B-CLL nuclear extracts was shown to bind to TRAF1 promoter elements. However, IκB kinase (IKK) activity was not increased in CLL lymphocytes as compared with normal CD19+ B cells. The known IKK inhibitor sulfasalazine did not compromise TRAF1 expression. Thus, although our study revealed a common expression pattern of NF-κB/Rel–regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL.

scholarly journals Coregulation of the APO-1 antigen with intercellular adhesion molecule- 1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2067-2075 ◽  
Author(s):  
P Moller ◽  
C Henne ◽  
F Leithauser ◽  
A Eichelmann ◽  
A Schmidt ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Adhesion Molecule ◽  
Tumor Necrosis ◽  
Plasma Cells ◽  
Intercellular Adhesion Molecule ◽  
Cross Linking ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor

Abstract APO-1 is a 48-Kd transmembrane glycoprotein identical to the Fas antigen and belongs to the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor family of surface molecules. Cross-linking of APO- 1 induces apoptotic cell death in sensitive cells. We show here that APO-1 is an activation molecule on B cells. It was induced/enhanced on dense and buoyant tonsillar B cells, respectively, through surface Ig cross-linking in combination with interleukin-2 or by interferon-gamma together with tumor necrosis factor-alpha. These conditions also increased the amount of intercellular adhesion molecule-1 (CD54) on these cells. Epstein-Barr virus transformants of peripheral B cells coexpressed APO-1 and CD54 at very high levels. Immunohistologically, Apo-1 was detectable at low levels in a subpopulation of follicle center B blasts and, at higher levels, in sinusoidal B cells. APO-1 was undetectable in follicular mantle B cells and plasma cells. In isolated tonsillar B cells, APO-1 was expressed in CD10+ follicle center cells. In acute B lymphoblastic leukemia, chronic B lymphocytic leukemia, and Burkitt's lymphomas, APO-1 and CD54 molecules were immunohistochemically undetectable. Coordinate expression of these antigens was found in mediastinal B-cell lymphomas. The mode of APO-1 and CD54 expression was correlated in follicle center cell lymphomas (P < .0019), but less stringently in hairy cell leukemia. No association was found in plasmacytomas. This was in line with the differential expression of these molecules found in reactive plasma cells. Expression of APO-1 in B cells of different stages of differentiation and, correspondingly, in certain B-cell neoplasias might suggest a role of this molecule in the induction of B-cell apoptosis. This function might be influenced by CD54 and CD54-mediated signals.

Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2948-2954 ◽  
Author(s):  
Kulwant Kaur ◽  
Shimul Chowdhury ◽  
Neil S. Greenspan ◽  
John R. Schreiber
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Antibody Responses ◽  
Preterm Neonates ◽  
Older Children ◽  
Humoral Immune ◽  
Encapsulated Bacteria ◽  
Necrosis Factor

AbstractNeonates have an increased rate of infection with encapsulated bacteria compared with older children and adults because of diminished antibody responses to T-independent (TI) antigens such as bacterial polysaccharides. Because the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody responses, we measured the expression of these receptors on adult and cord blood–derived term and preterm neonatal B cells. Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and had significantly less proliferation compared with adult B cells after stimulation with human recombinant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation. In addition, neonatal dendritic cells had diminished expression of B7–1, B7–2, and CD40 compared with adult cells. Finally, neonatal B cells, particularly preterm B cells, exhibited markedly decreased production of IgG and IgA in response to CD40L and IL-10. Overall, this study shows that maturational delay in TNFR expression particularly by preterm neonatal B cells may interfere with effective antibody responses to TI antigens, cognate T- and B-cell interactions and normal isotype switching.

scholarly journals B Cell Production of Tumor Necrosis Factor in Response to Pneumocystis murina Infection in Mice

2013 ◽  
Vol 81 (11) ◽  
pp. 4252-4260 ◽  
Author(s):  
Michael M. Opata ◽  
Zhan Ye ◽  
Melissa Hollifield ◽  
Beth A. Garvy
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Fungal Pathogens ◽  
Tumor Necrosis ◽  
Early Time ◽  
Primary Response ◽  
Content Type ◽  
Necrosis Factor

ABSTRACTPneumocystisspecies are opportunistic fungal pathogens that induce tumor necrosis factor (TNF) production by alveolar macrophages. Here we report that B cells from the draining lymph nodes as well as lung CD4+T cells are important producers of TNF uponPneumocystis murinainfection. To determine the importance of B cell-derived TNF in the primary response toP. murina, we generated bone marrow chimeras whose B cells were unable to produce TNF. The lungP. murinaburden at 10 days postinfection in TNF knockout (TNFKO) chimeras was significantly higher than that in wild-type (WT) chimeras, which corresponded to reduced numbers of activated CD4+T cells in the lungs at this early time point. Furthermore, CD4+T cells isolated fromP. murina-infected TNFKO chimeras were unable to stimulate clearance ofP. murinaupon adoptive transfer to recombinase-deficient (RAG1KO) hosts. Together, these data indicate that B cell-derived TNF plays an important function in promoting CD4+T cell expansion and production of TNF and facilitating protection againstP. murinainfection.

scholarly journals Generation of Splenic Follicular Structure and B Cell Movement in Tumor Necrosis Factor–deficient Mice

1998 ◽  
Vol 188 (8) ◽  
pp. 1503-1510 ◽  
Author(s):  
Matthew C. Cook ◽  
Heinrich Körner ◽  
D. Sean Riminton ◽  
Frances A. Lemckert ◽  
Jhagvaral Hasbold ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Cell Movement ◽  
Wild Type ◽  
Germinal Center Reaction ◽  
Necrosis Factor

Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin α (LTα). The role of TNF in B cell positioning and formation of follicular structure was studied by comparing the location of newly produced naive recirculating and antigen-stimulated B cells in TNF−/− and TNF/LTα−/− mice. By creating radiation bone marrow chimeras from wild-type and TNF−/− mice, formation of normal splenic B cell follicles was shown to depend on TNF production by radiation-sensitive cells of hemopoietic origin. Reciprocal adoptive transfers of mature B cells between wild-type and knockout mice indicated that normal follicular tropism of recirculating naive B cells occurs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor–IgG fusion protein administered in vivo failed to prevent B cell localization to the follicle or the germinal center reaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF−/− recipients, but not into TNF/LTα−/− recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTα−/− mice because TNF/LTα−/− B cells, when stimulated in vitro, switched isotypes normally. Thus, TNF is necessary for creating the permissive environment for B cell movement and function, but is not itself responsible for these processes.

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