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

scholarly journals B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Eric E Irons ◽  
Melissa M Lee-Sundlov ◽  
Yuqi Zhu ◽  
Sriram Neelamegham ◽  
Karin M Hoffmeister ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitors ◽  
Myeloma Cells ◽  
Human B Cells ◽  
Extrinsic Cues ◽  
Bone Marrow Niches ◽  
Dependent Mechanism

The immune response relies on the integration of cell-intrinsic processes with cell-extrinsic cues. During infection, B cells vacate the marrow during emergency granulopoiesis but return upon restoration of homeostasis. Here we report a novel glycosylation-mediated crosstalk between marrow B cells and hematopoietic progenitors. Human B cells secrete active ST6GAL1 sialyltransferase that remodels progenitor cell surface glycans to suppress granulopoiesis. In mouse models, ST6GAL1 from B cells alters the sialylation profile of bone marrow populations, and mature IgD+ B cells were enriched in sialylated bone marrow niches. In clinical multiple myeloma, ST6GAL1 abundance in the multiple myeloma cells negatively correlated with neutrophil abundance. These observations highlight not only the ability of medullary B cells to influence blood cell production, but also the disruption to normal granulopoiesis by excessive ST6GAL1 in malignancy.

Mesenchymal stem cells from bone marrow of rheumatoid arthritis patients provide survival signals to T- and B- cells in vitro

2007 ◽  
Vol 74 (2) ◽  
pp. S217 ◽  
Author(s):  
Tomas Dallos ◽  
Monika Krivosikova ◽  
Lukasz Luszczyna ◽  
Magdalena Chorazy-Massalska ◽  
Ewa Warnawin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
T And B Cells ◽  
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.

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.

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

Increased Survival and Migration of CLL B-Cells in the Presence of Marrow Mesenchymal Stromal Cells: Novel Findings for Microenvironment-Targeted Therapies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4571-4571
Author(s):  
Elisa Ave ◽  
Federica Frezzato ◽  
Cristina Gattazzo ◽  
Valentina Trimarco ◽  
Veronica Martini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Stromal Cells ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Spontaneous Apoptosis ◽  
Parp 1 ◽  
Cells Cultured ◽  
Survival Signals

Abstract Abstract 4571 Background. The accumulation of CD19+/CD5+/CD23+ B cells with a prolonged lifespan in peripheral blood, secondary lymphoid organs and bone marrow (BM) is a peculiar feature of B-cell chronic lymphocytic leukemia (B-CLL). Since CLL cells removed from the in vivo microenvironment and in vitro cultured rapidly undergo spontaneous apoptosis, bidirectional interactions between malignant and by-stander cells may lead to an abnormal microenvironment that confers growth advantages to neoplastic clone. Mesenchymal Stromal Cells (MSCs) are the dominant marrow stromal population in indolent subtype of CLL/small lymphocytic leukemia (SLL) and follicular lymphoma (FL), rather than other aggressive B-cell lymphomas, and are involved in B-CLL cell survival. Despite the phenotypic and cytologic homogeneity, CLL is characterized by extremely variable clinical courses, suggesting that malignant B-cells hold variable degrees of dependency on pro-survival signals coming from the microenvironment. The aim of this study was to assess the role of MSCs in CLL B-cell localization and survival, defining the degree of dependency of leukemic B-cells from external pro-survival signals, with the ultimate goal of identifying patients that mostly benefit microenvironment-targeted therapies. Methods. MSCs isolated from the BM of 47 B-CLL patients were expanded ex vivo and characterized through flow cytometry analysis and differentiation cultures. Fresh isolated CLL peripheral blood mononuclear cells were co-cultured with CLL-MSCs or stromal cells and apoptosis were measured by Annexin V test and western blotting analysis (PARP-1 detection). Chemotactic assays were performed. Results. The survival of neoplastic cells ranged from 13.3% (±13.2) in leukemic cells cultured in medium alone to 58.5% (±17.2) when leukemic cells were cultured in presence of CLL-MSCs (p<0.01). Transwell experiments showed that the anti-apoptotic effect is mediated by soluble factors produced by MSCs. We investigated whether different CLL clones show a different susceptibility to spontaneous apoptosis when co-cultured in presence of MSCs recovered from B-CLL patients. The detection of the 85KDa cleaved PARP fragment in all CLL B-cells cultured in medium alone confirmed that they underwent spontaneous apoptosis. At the same time, the presence or the lacking of the cleaved fragment of PARP-1 on CLL B-cells after 7 day-co-cultures with MSCs discriminated patients into two groups: non-responder (89 kDa Parp fragment detectable) and responder (89 kDa Parp fragment not detectable) to microenvironment pro-survival signals. Finally, chemotaxis tests showed the ability of MSCs to produce and release molecules promoting the migration and the localization of neoplastic B-cells in bone marrow (Migration Index of leukemic cells: 5.1; Migration Index of normal B cells: 1.9; p<0.01). Conclusions. MSCs derived from patients with B-CLL provide survival signals to neoplastic cells, extending their lifespan and producing chemotactic factors that favour their accumulation into BM. On the other hand, CLL cells display heterogeneous responses to environmental pro-survival signals, suggesting that each CLL clone could differently react to the microenvironment protection. The blocking of the cross-talk between malignant clone and accessory cells within the microenvironment might represent an attractive novel strategy for CLL therapy. Our data provide the rationale for tailored therapies which powerfully target the cross-talk with marrow cells, particularly on patients carrying a clone more sensitive to anti-apoptotic signals coming from the microenvironment. Disclosures: No relevant conflicts of interest to declare.

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