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 TRANCE (Tumor Necrosis Factor [TNF]-related Activation-induced Cytokine), a New TNF Family Member Predominantly Expressed in T cells, Is a Dendritic Cell–specific Survival Factor

1997 ◽  
Vol 186 (12) ◽  
pp. 2075-2080 ◽  
Author(s):  
Brian R. Wong ◽  
Régis Josien ◽  
Soo Young Lee ◽  
Birthe Sauter ◽  
Hong-Li Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Dominant Negative ◽  
Mouse Bone Marrow ◽  
Survival Factor ◽  
Necrosis Factor

TRANCE (tumor necrosis factor [TNF]–related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor–associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow–derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-xL expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival of T or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell–DC communication and may provide a tool to selectively enhance DC activity.

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 Tumor Necrosis Factor Alpha Production from CD8+T Cells Mediates Oviduct Pathological Sequelae following Primary Genital Chlamydia muridarum Infection

2011 ◽  
Vol 79 (7) ◽  
pp. 2928-2935 ◽  
Author(s):  
Ashlesh K. Murthy ◽  
Weidang Li ◽  
Bharat K. R. Chaganty ◽  
Sangamithra Kamalakaran ◽  
M. Neal Guentzel ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTThe immunopathogenesis ofChlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin−/−mice) or tumor necrosis factor alpha (TNF-α) production (TNF-α−/−mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-α are effector mechanisms of CD8+T cells, we evaluated the role of CD8+T cells during genitalChlamydia muridaruminfection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8+T cells), (ii) wild-type mice depleted of CD8+T cells, and (iii) mice genetically deficient in CD8 (CD8−/−mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8+T cells in chlamydial pathogenesis. Repletion of CD8−/−mice with wild-type or perforin−/−, but not TNF-α−/−, CD8+T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8+T cells is important for pathogenesis. Additionally, repletion of TNF-α−/−mice with TNF-α+/+CD8+T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α−/−mice but not to the levels found in wild-type mice, suggesting that TNF-α production from CD8+T cells and non-CD8+cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8+T cells and TNF-α production toChlamydia-induced reproductive tract sequelae.

scholarly journals Tumor Necrosis Factor Alpha Antagonism Reveals a Gut/Lung Axis That Amplifies Regulatory T Cells in a Pulmonary Fungal Infection

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Jamie L. Tweedle ◽  
George S. Deepe
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Regulatory T Cells ◽  
Tumor Necrosis ◽  
Histoplasma Capsulatum ◽  
Inflammatory Diseases ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Necrosis Factor

ABSTRACTTumor necrosis factor (TNF) antagonists are popular therapies for inflammatory diseases. These agents enhance the numbers and function of regulatory T cells (Tregs), which are important in controlling inflammatory diseases. However, elevated Treg levels increase susceptibility to infections, including histoplasmosis. We determined the mechanism by which Tregs expand in TNF-neutralized mice infected withHistoplasma capsulatum. Lung CD11c+CD11b+dendritic cells (DCs), but not alveolar macrophages, fromH. capsulatum-infected mice treated with anti-TNF induced a higher percentage of Tregs than control DCsin vitro. CD11b+CD103+DCs, understood to be unique to the intestines, were augmented in lungs with anti-TNF treatment. In the absence of this subset, DCs from anti-TNF-treated mice failed to amplify Tregsin vitro. CD11b+CD103+DCs from TNF-neutralized mice displayed higher retinaldehyde dehydrogenase 2 (RALDH2) gene expression, and CD11b+CD103+RALDH+DCs exhibited greater enzyme activity. To determine if CD11b+CD103+DCs migrated from gut to lung, fluorescent beads were delivered to the gut via oral gavage, and the lungs were assessed for bead-containing DCs. Anti-TNF induced migration of CD11b+CD103+DCs from the gut to the lung that enhanced the generation of Tregs inH. capsulatum-infected mice. Therefore, TNF neutralization promotes susceptibility to pulmonaryH. capsulatuminfection by promoting a gut/lung migration of DCs that enhances Tregs.

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 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.

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