Increased NF-κB activity in B?cells and bone marrow-derived dendritic cells from NOD mice

2004 ◽  
Vol 34 (5) ◽  
pp. 1395-1404 ◽  
Author(s):  
William Wheat ◽  
Rene Kupfer ◽  
Diane?G. Gutches ◽  
Gina?R. Rayat ◽  
Joshua Beilke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
B Cells ◽  
Nod Mice

Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches

2008 ◽  
Vol 9 (4) ◽  
pp. 388-395 ◽  
Author(s):  
Anita Sapoznikov ◽  
Yael Pewzner-Jung ◽  
Vyacheslav Kalchenko ◽  
Rita Krauthgamer ◽  
Idit Shachar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
B Cells ◽  
Bone Marrow Niches ◽  
Critical Survival ◽  
Survival Signals

Modulation of murine bone marrow-derived dendritic cells and B-cells by MCS-18 a natural product isolated from Helleborus purpurascens

Immunobiology ◽  
2008 ◽  
Vol 213 (9-10) ◽  
pp. 871-878 ◽  
Author(s):  
Leonie Littmann ◽  
Susanne Rößner ◽  
Franz Kerek ◽  
Alexander Steinkasserer ◽  
Elisabeth Zinser
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
B Cells ◽  
Natural Product ◽  
Murine Bone Marrow

scholarly journals Thymic Overexpression of CD40 Ligand Disrupts Normal Thymic Epithelial Organization

1997 ◽  
Vol 45 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Robert J. Dunn ◽  
Carrie J. Luedecker ◽  
Harald S. Haugen ◽  
Christopher H. Clegg ◽  
Andrew G. Farr
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
B Cells ◽  
Epithelial Cells ◽  
Bone Marrow Cells ◽  
Cd40 Ligand ◽  
Epithelial Differentiation ◽  
Location Analysis ◽  
Normal Pattern ◽  
Cd40 Expression

We characterized the distribution of CD40 and CD40 ligand (CD40-L) in the adult and developing murine thymus. Before birth, CD40 was almost exclusively localized to scattered foci of medullary cells. By birth there was a dramatic upregulation of CD40 expression by cortical epithelial cells, which was accompanied by a consolidation of medullary epithelial foci. CD40-L+ thymocytes displayed a medullary location. Analysis of mice deficient in CD40-L expression indicated that CD40-L/CD40 interactions were not required for development of the medullary compartment. Overexpression of CD40-L targeted to thymocytes altered thymic architecture, as reflected by a dramatic loss of cortical epithelial cells, expansion of the medullary compartment, and extensive infiltration of the capsule with a mixture of CD3+ cells, B-cells, and macrophages/dendritic cells. Reconstitution of lethally irradiated normal mice with lck CD40-L bone marrow cells also resulted in loss of cortical epithelium and expansion of the medullary compartment. Disruption of the normal pattern of thymic architecture and epithelial differentiation as a consequence of increased intrathymic levels of CD40-L expression points to a role for CD40-L/CD40 interactions in the normal pattern of epithelial compartmentalization/differentiation within the thymic environment.

scholarly journals Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

1998 ◽  
Vol 188 (3) ◽  
pp. 451-463 ◽  
Author(s):  
Christoph Schaniel ◽  
Evangelia Pardali ◽  
Federica Sallusto ◽  
Mattheos Speletas ◽  
Christiane Ruedl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Amino Acid ◽  
B Cells ◽  
B Lymphocytes ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Splenic Cells

Genes were isolated using the suppression subtractive hybridization method by stimulation of pro/pre B cells with anti-CD40 and interleukin (IL)-4 to mature Sμ-Sε–switched cells. One of the strongly upregulated genes encodes a novel murine CC chemokine we have named ABCD-1. The ABCD-1 gene has three exons separated by 1.2- and 2.7-kb introns. It gives rise to a 2.2-kb transcript containing an open reading frame of 276 nucleotides. Two polyadenylation sites are used, giving rise to cDNAs with either 1550 or 1850 bp of 3′ untranslated regions. The open reading frame encodes a 24 amino acid–long leader peptide and a 68 amino acid–long mature protein with a predicted molecular mass of 7.8 kD. ABCD-1 mRNA is found in highest quantities in activated splenic B lymphocytes and dendritic cells. Little chemokine mRNA is present in lung, in unstimulated splenic cells, in thymocytes, and in lymph node cells. No ABCD-1 mRNA is detected in bone marrow, liver, kidney, or brain, in peritoneal exudate cells as well as in the majority of all unstimulated B lineage cells tested. It is also undetectable in Concanavalin A–activated/IL-2–restimulated splenic T cells, and in bone marrow–derived IL-2–induced natural killer cells and IL-3–activated macrophages. Recombinant ABCD-1 revealed a concentration-dependent and specific migration of activated splenic T lymphoblasts in chemotaxis assays. FACS® analyses of migrated cells showed no preferential difference in migration of CD4+ versus CD8+ T cell blasts. Murine as well as human T cells responded to ABCD-1. Freshly isolated cells from bone marrow, thymus, spleen, and lymph node, IL-2–activated NK cells, and LPS-stimulated splenic cells, all did not show any chemotactic response. Thus, ABCD-1 is the first chemokine produced in large amounts by activated B cells and acting selectively on activated T lymphocytes. Therefore, ABCD-1 is expected to play an important role in the collaboration of dendritic cells and B lymphocytes with T cells in immune responses.

Immunotherapy of NOD mice with bone marrow-derived dendritic cells

Diabetes ◽  
1999 ◽  
Vol 48 (12) ◽  
pp. 2300-2308 ◽  
Author(s):  
M. Feili-Hariri ◽  
X. Dong ◽  
S. M. Alber ◽  
S. C. Watkins ◽  
R. D. Salter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Nod Mice

GM-CSF induces bone marrow precursors of NOD mice to skew into tolerogenic dendritic cells that protect against diabetes

2010 ◽  
Vol 265 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Simon Gaudreau ◽  
Chantal Guindi ◽  
Michaël Ménard ◽  
Ahmed Benabdallah ◽  
Gilles Dupuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Nod Mice ◽  
Gm Csf ◽  
Tolerogenic Dendritic Cells

Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5644-5649 ◽  
Author(s):  
Kate A. Markey ◽  
Tatjana Banovic ◽  
Rachel D. Kuns ◽  
Stuart D. Olver ◽  
Alistair L. J. Don ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Transplantation ◽  
B Cells ◽  
Marrow Transplantation ◽  
Significant Contribution ◽  
Therapeutic Strategies ◽  
Relative Contribution ◽  
Histocompatibility Complex ◽  
Antigen Presenting

We have quantified the relative contribution of donor antigen-presenting cell populations to alloantigen presentation after bone marrow transplantation (BMT) by using transgenic T cells that can respond to host-derived alloantigen presented within the donor major histocompatibility complex. We also used additional transgenic/knockout donor mice and/or monoclonal antibodies that allowed conditional depletion of conventional dendritic cells (cDCs), plasmacytoid DC (pDCs), macrophages, or B cells. Using these systems, we demonstrate that donor cDCs are the critical population presenting alloantigen after BMT, whereas pDCs and macrophages do not make a significant contribution in isolation. In addition, alloantigen presentation was significantly enhanced in the absence of donor B cells, confirming a regulatory role for these cells early after transplantation. These data have major implications for the design of therapeutic strategies post-BMT, and suggest that cDC depletion and the promotion of B-cell reconstitution may be beneficial tools for the control of alloreactivity.

scholarly journals Elucidating Role of Ezh2 in Tolerogenic Function of NOD Bone Marrow-Derived Dendritic Cells Expressing Constitutively Active Stat5b.

2019 ◽  
Author(s):  
Echarki Zerif ◽  
Denis Gris ◽  
Gilles Dupuis ◽  
Abdelaziz Amrani
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Transgenic Mice ◽  
Molecular Mechanisms ◽  
Active Form ◽  
Nod Mice ◽  
Autoreactive T Cell ◽  
Tolerogenic Function ◽  
Constitutively Active

Tolerogenic dendritic cells are crucial to control development of autoreactive T cell responses and prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active form of Stat5b under the control of CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function is not fully understood. Here, we used bone marrow-derived DCs from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDC) and found that Stat5b-CA.BMDC displayed high levels of MHC class II, CD80, CD86, PD-L1 and PD-L2 and produced elevated amounts of TGFβ but low amounts of TNF and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 interacted with Stat5b-CA complex that bound GAS sequences in the Irf8 enhancer whereas Ezh2 did not interact with GAS sequences in the case of the Irf4 promoter. Injection of Stat5b-CA.BMDCs to prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DCs function.

scholarly journals Activation of Toll-Like Receptor 7 Signaling Pathway in Primary Sjögren's Syndrome-Associated Thrombocytopenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuo Zhang ◽  
Jingge Qu ◽  
Li Wang ◽  
Mengtao Li ◽  
Dong Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Signaling Pathway ◽  
High Throughput ◽  
Nod Mice ◽  
Primary Sjögren’S Syndrome ◽  
Toll Like Receptor ◽  
Control Groups ◽  
Platelet Counts ◽  
And Control

Objectives: To identify the importance of the Toll-like receptor (TLR) pathway using B cell high-throughput sequencing and to explore the participation of the TLR7 signaling pathway in primary Sjogren's syndrome (pSS)-associated thrombocytopenia in patient and mouse models.Methods: High-throughput gene sequencing and bioinformatic analyses were performed for 9 patients: 3 patients with pSS and normal platelet counts, 3 patients with pSS-associated thrombocytopenia, and 3 healthy controls. Twenty-four patients with pSS were recruited for validation. Twenty-four non-obese diabetic (NOD) mice were divided into the TLR7 pathway inhibition (CA-4948), activation (Resiquimod), and control groups. Serum, peripheral blood, bone marrow, and submandibular glands were collected for thrombocytopenia and TLR7 pathway analysis.Results: Seven hub genes enriched in the TLR pathway were identified. Compared to that in control patients, the expression of interleukin (IL)-8 and TLR7 pathway molecules in B-cells was higher in patients with pSS-associated thrombocytopenia. Platelet counts exhibited a negative correlation with serum IL-1β and IL-8 levels. In NOD mice, CA-4948/Resiquimod treatment induced the downregulation/upregulation of the TLR7 pathway, leading to consistent elevation/reduction of platelet counts. Megakaryocyte counts in the bone marrow showed an increasing trend in the Resiquimod group, with more naked nuclei. The levels of IL-1β and IL-8 in the serum and submandibular gland tissue increased in the Resiquimod group compared with that in CA-4948 and control groups.Conclusion: pSS-associated thrombocytopenia may be a subset of the systemic inflammatory state as the TLR7 signaling pathway was upregulated in B cells of patients with pSS-associated thrombocytopenia, and activation of the TLR7 pathway led to a thrombocytopenia phenotype in NOD mice.

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