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.

J-LEAPS Vaccines Mature Mouse Bone Marrow Cells to Dendritic Cells-1 (DC1) which can Deliver Protective Immunity

2010 ◽  
Vol 135 ◽  
pp. S32
Author(s):  
Patricia Taylor ◽  
Gary Koski ◽  
Erin Bailey ◽  
Daniel Zimmerman ◽  
Ken S. Rosenthal
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Protective Immunity ◽  
Bone Marrow Cells ◽  
Mouse Bone Marrow ◽  
Mature Mouse ◽  
Mouse Bone Marrow Cells ◽  
Marrow Cells

Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages

1990 ◽  
Vol 10 (7) ◽  
pp. 3562-3568
Author(s):  
M Principato ◽  
J L Cleveland ◽  
U R Rapp ◽  
K L Holmes ◽  
J H Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Hematopoietic Differentiation ◽  
Developmental Relationships ◽  
Murine Bone Marrow ◽  
B Lineage ◽  
Marrow Cells

Murine bone marrow cells infected with replication-defective retroviruses containing v-raf alone or v-myc alone yielded transformed pre-B cell lines, while a retroviral construct containing both v-raf and v-myc oncogenes produced clonally related populations of mature B cells and mature macrophages. The genealogy of these transformants demonstrates that mature myeloid cells were derived from cells with apparent B-lineage commitment and functional immunoglobulin rearrangements. This system should facilitate studies of developmental relationships in hematopoietic differentiation and analysis of lineage determination.

scholarly journals Heme-stress activated NRF2 skews fate trajectories of bone marrow cells from dendritic cells towards red pulp-like macrophages in hemolytic anemia

2022 ◽  
Author(s):  
Florence Vallelian ◽  
Raphael M. Buzzi ◽  
Marc Pfefferlé ◽  
Ayla Yalamanoglu ◽  
Irina L. Dubach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Sickle Cell Disease ◽  
Bone Marrow Cells ◽  
Cell Disease ◽  
Secondary Immunodeficiency ◽  
Gm Csf ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

AbstractHeme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias, such as sickle cell disease. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Since chronic heme-stress is noxious for macrophages, erythrophagocytes in the spleen are continuously replenished from bone marrow-derived progenitors. Here, we hypothesized that adaptation to heme stress progressively shifts differentiation trajectories of bone marrow progenitors to expand the capacity of heme-handling monocyte-derived macrophages at the expense of the homeostatic generation of dendritic cells, which emerge from shared myeloid precursors. This heme-induced redirection of differentiation trajectories may contribute to hemolysis-induced secondary immunodeficiency. We performed single-cell RNA-sequencing with directional RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation of bone marrow cells towards antioxidant, iron-recycling macrophages, suppressing the generation of dendritic cells in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific CD4 T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype of macrophage expansion with concurrent dendritic cell depletion was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning of hemolytic stress as a driver of hyposplenism-related secondary immunodeficiency.

scholarly journals The Effect of Influenza Vaccines on Maturation of Dendritic Cells Generated from Bone Marrow

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Kostinova AM ◽  
◽  
Yukhacheva DV ◽  
Akhmatova EA ◽  
Akhmatova NK ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Influenza Vaccines ◽  
Human Bone Marrow ◽  
Vitro Model ◽  
Cytokine Stimulation ◽  
Marrow Cells

Background: Possibility to control immune system by regulating the activity of Dendritic Cells (DC) with the help of vaccines or other immunobiological drugs opens great prospects for infectious, oncological and autoimmune control. The aim of this study was to evaluate in vitro the effect of adjuvant subunit and non-adjuvant split influenza vaccines on maturation of DCs from human bone marrow. Methods: From bone marrow cells of healthy volunteers, DCs were obtained using rGM-CSF and IL-4. On the 8th day of cultivation, 10μl of vaccines against influenza were introduced into the culture of Immature DCs (i-DCs): a non-adjuvant split vaccine (Vaxigripp, Sanofi Pasteur) and an immunoadjuvant subunit vaccine (Grippol plus, Petrovax), as well as immunomodulator Polyoxidonium. Results: Insertion of influenza vaccines into i-DC culture induced the acquisition by DCs typical morphological signs of maturation. DCs became large with eccentrically located of irregular shape nucleus, densified cytoplasm, numerous processes. By immunophenotypic examination decrease in monocyte/macrophage pool, cells with expression of CD34 immaturity marker, increase in expressing CD11c/CD86 costimulatory molecules and CD83 terminal differentiation molecules were observed. Although Polyoxidonium caused a decrease in number of CD11c/CD14 cells (18, 5%), but compared to vaccines, its activity was lower (p<0, 05). Grippol plus more actively induced differentiation of TLR2 and TLR8 expressing cells, whereas Vaxigripp-expression of TLR4 and TLR8 on DCs. Conclusion: The possibility of using in vitro model of DCs obtained from human bone marrow cells by cytokine stimulation for examination of the ability of influenza vaccines to induce DC maturation processes has been demonstrated.

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 Differentiation of dendritic cells in cultures of rat bone marrow cells.

1986 ◽  
Vol 163 (4) ◽  
pp. 872-883 ◽  
Author(s):  
W E Bowers ◽  
M R Berkowitz
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Cells ◽  
Sensitive Assay ◽  
Ia Antigens ◽  
Bone Marrow Cultures ◽  
Nonadherent Cells ◽  
Marrow Cultures ◽  
Rat Bone ◽  
Marrow Cells

Although dendritic cells (DC) originate from bone marrow, they were not observed in fresh preparations of bone marrow cells (BMC). Likewise, accessory activity was barely measurable in a sensitive assay for this potent function of DC. However, both DC and accessory activity developed when BMC were cultured for 5 d. Based on fractionation before culture, nearly all of the accessory activity could be attributed to only 5% of the total BMC recovered in a low-density (LD) fraction. The LD-DC precursors differed from mature DC in a number of important respects. Removal of Ia+ cells from the LD fraction by panning did not decrease the production of DC when the nonadherent cells were cultured. Thus, the cell from which the DC is derived does not express or minimally expresses Ia antigens, in contrast to the strongly Ia+ DC that is produced in bone marrow cultures. Irradiation of LD cells before culture prevented the development of DC. When irradiation was delayed by daily intervals, progressive increases in the number of DC resulted, up to the fifth day. These findings, together with preliminary autoradiographic data, indicate that cell division has occurred, in contrast to the DC, which does not divide. We conclude that bone marrow-derived DC arise in culture from the division of LD, Ia- precursors.

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