Cell type-dependent difference in the distribution and frequency of aphidicolin-induced fragile sites: T and B lymphocytes and bone marrow cells

1989 ◽  
Vol 84 (1) ◽  
pp. 71-74 ◽  
Author(s):  
Ichiro Murano ◽  
Akira Kuwano ◽  
Tadashi Kajii
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Fragile Sites ◽  
T And B Lymphocytes ◽  
Cell Type ◽  
Marrow Cells

scholarly journals Defective lymphopoiesis in bone marrow of motheaten (me/me) and viable motheaten (mev/mev) mutant mice. I. Analysis of development of prothymocytes, early B lineage cells, and terminal deoxynucleotidyl transferase-positive cells.

1986 ◽  
Vol 164 (4) ◽  
pp. 1129-1144 ◽  
Author(s):  
D L Greiner ◽  
I Goldschneider ◽  
K L Komschlies ◽  
E S Medlock ◽  
F J Bollum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Precursor Cells ◽  
T And B Lymphocytes ◽  
Normal Numbers ◽  
B Lineage ◽  
Marrow Cells ◽  
B Lineage Cells

This study identifies defects in the early stages of lymphopoiesis that may contribute to the abnormalities in the development and/or function of peripheral T and B lymphocytes in mice homozygous for the motheaten (me/me) and viable motheaten (mev/mev) mutations. The results indicate that in me/me and mev/mev mice prothymocytes in bone marrow are present in essentially normal numbers, as determined by intrathymic injection, but apparently lack the ability to home effectively to the thymus, as determined by intravenous transfer; early B lineage cells in bone marrow, identified by the B220 antigen, are markedly depleted, including immature B cells (sIg+), pre-B cells (cIg+, sIg-), and pro-B cells (B220+, cIg-, sIg-); TdT+ bone marrow cells, especially a subset that expresses the B220 B lineage antigen, are markedly depleted by two weeks of age; normal numbers of TdT+ thymocytes are present during the first 3 wk of postnatal life, but rapidly decrease thereafter. The results further indicate that neither the defective thymus homing capacity of prothymocytes nor the deficiency of TdT+ bone marrow cells is due to autoantibodies. The possible relationship of the defective development of lymphoid precursor cells to the premature onset of thymic involution and to the abnormalities of peripheral T and B lymphocytes in me/me and mev/mev mice is discussed; as are the results of in vitro studies (presented in a companion paper), which suggest that a primary defect in the stromal microenvironment of the bone marrow is responsible for the abnormal development of the lymphoid precursor cells.

scholarly journals THE ROLE OF THYMUS AND BONE MARROW CELLS IN DELAYED HYPERSENSITIVITY

1971 ◽  
Vol 134 (5) ◽  
pp. 1144-1154 ◽  
Author(s):  
David G. Tubergen ◽  
Joseph D. Feldman
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Cell Type ◽  
Skin Reactions ◽  
Lymph Node Cells ◽  
Thymus Cells ◽  
Marrow Cells

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.

scholarly journals Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 368-379 ◽  
Author(s):  
Jinyong Wang ◽  
Yangang Liu ◽  
Zeyang Li ◽  
Zhongde Wang ◽  
Li Xuan Tan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Lymphoblastic Leukemia ◽  
Marrow Transplant ◽  
Dependent Manner ◽  
Myeloproliferative Disease ◽  
Cell Type ◽  
Nras Mutation ◽  
Secretase Inhibitor ◽  
Marrow Cells

Abstract Both monoallelic and biallelic oncogenic NRAS mutations are identified in human leukemias, suggesting a dose-dependent role of oncogenic NRAS in leukemogenesis. Here, we use a hypomorphic oncogenic Nras allele and a normal oncogenic Nras allele (Nras G12Dhypo and Nras G12D, respectively) to create a gene dose gradient ranging from 25% to 200% of endogenous Nras G12D/+. Mice expressing Nras G12Dhypo/G12Dhypo develop normally and are tumor-free, whereas early embryonic expression of Nras G12D/+ is lethal. Somatic expression of Nras G12D/G12D but not Nras G12D/+ leads to hyperactivation of ERK, excessive proliferation of myeloid progenitors, and consequently an acute myeloproliferative disease. Using a bone marrow transplant model, we previously showed that ∼ 95% of animals receiving Nras G12D/+ bone marrow cells develop chronic myelomonocytic leukemia (CMML), while ∼ 8% of recipients develop acute T-cell lymphoblastic leukemia/lymphoma [TALL] (TALL-het). Here we demonstrate that 100% of recipients transplanted with Nras G12D/G12D bone marrow cells develop TALL (TALL-homo). Although both TALL-het and -homo tumors acquire Notch1 mutations and are sensitive to a γ-secretase inhibitor, endogenous Nras G12D/+ signaling promotes TALL through distinct genetic mechanism(s) from Nras G12D/G12D. Our data indicate that the tumor transformation potential of endogenous oncogenic Nras is both dose- and cell type-dependent.

Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization Of Hematopoietic Stem- and Progenitor Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2460-2460
Author(s):  
Evert-Jan F. M. de Kruijf ◽  
Ingmar van Hengel ◽  
Jorge M Perez-Galarza ◽  
Willem E. Fibbe ◽  
Melissa van Pel
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Calf Serum ◽  
Intraperitoneal Administration ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract Hematopoietic stem- and progenitor cell (HSPC) mobilization is a property of most hematopoietic growth factors, such as Granulocyte Colony Stimulating Factor (G-CSF). Not all donors mobilize equally well and therefore the number of HSPC that are obtained following mobilization may be limited. Mesenchymal stromal cells (MSC) have the capacity to differentiate into cells of the mesodermal lineage and have immunomodulatory properties in vivo and in vitro. Here, we have investigated the effect of MSC co-administration on G-CSF-induced HSPC mobilization. MSC were obtained from bone marrow cells (bone marrow-derived) or bone fragments (bone-derived) and were expanded in alpha-MEM containing 10% fetal calf serum until sufficient cell numbers were obtained. Bone marrow or bone-derived MSC were administered intravenously for three days at a dose of 200 x103 cells per day to male C57BL/6 recipients that were simultaneously mobilized with G-CSF (10 μg per day intraperitoneally for 3 days) or PBS as a control. Co-injection of G-CSF and MSC lead to a 2-fold increase in HSPC mobilization compared to G-CSF alone (8,563 ± 3,309 vs. 4,268 ± 1,314 CFU-C per ml peripheral blood respectively; n=13, p<0.01). Administration of MSC alone did not induce HSPC mobilization (273 ± 229 CFU-C/ml blood; n=13). Furthermore, co-injection of splenocytes and G-CSF did not enhance HSPC mobilization, showing that the administration of exogeneous cells as such is not sufficient for enhancement of HSPC mobilization. It has been reported that G-CSF-induced HSPC mobilization is associated with a decrease in the number of osteal macrophages, B lymphocytes and erythroid progenitors. Administration of MSC alone induced a significant decrease in the frequency of osteal macrophages (7.9 ± 1.2 vs 6.2 ± 1.4% bone marrow cells for PBS vs. MSC respectively; n=8, p<0.05), but did not affect osteoblast numbers. Furthermore, the frequency of B lymphocytes was significantly decreased following MSC administration (29.9 ± 4.0 vs. 16.5 ± 4.9% bone marrow cells for PBS vs. MSC respectively; n=13, p<0.0001). No differences were observed in erythroid numbers following MSC administration. To investigate the mechanisms underlying these observations, the migratory capacity of luciferase transduced MSC was studied through bioluminescence imaging. Following intravenous injection, MSC were detected in the lungs, but not in other organs. In addition, no difference in MSC migration was observed between G-CSF and PBS treated mice. Moreover, intraperitoneal administration of G-CSF and MSC resulted in increased HSPC mobilization compared to G-CSF alone (10,178 ±3,039 vs. 5,158 ± 2,436 CFU-C per ml peripheral blood; n=5-12). Together, these data point to an endocrine effect of MSC on G-CSF-induced HSPC mobilization. No differences in IL-6, CXCL-12 or M-CSF levels in bone marrow extracellular fluid were observed. In conclusion, G-CSF-induced HSPC mobilization is enhanced by injection of MSC. We hypothesize that the MSC-induced partial depletion of B lymphocytes and osteal macrophages in the bone marrow are crucial factors involved in the enhancement of G-CSF-induced HSPC mobilization. Disclosures: No relevant conflicts of interest to declare.

scholarly journals THE LIFE-SPAN AND RECIRCULATION OF MARROW-DERIVED SMALL LYMPHOCYTES FROM THE RAT THORACIC DUCT

1972 ◽  
Vol 135 (2) ◽  
pp. 185-199 ◽  
Author(s):  
Jonathan C. Howard
Keyword(s):  
Bone Marrow ◽  
Life Span ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Thoracic Duct Lymph ◽  
Clear Cut ◽  
Duct Lymph ◽  
Order Of Magnitude ◽  
Marrow Cells

These experiments describe the preparation of pure marrow-derived lymphocyte suspensions from the thoracic duct of thymectomized, irradiated rats reconstituted with bone marrow cells. The majority of marrow-derived cells were small lymphocytes morphologically indistinguishable from small lymphocytes in thoracic duct lymph of normal donors. Marrow-derived small lymphocytes (B lymphocytes) were a predominantly long-lived population; the frequency of short-lived B lymphocytes in the thoracic duct was not significantly higher than the frequency of short-lived small lymphocytes in normal lymph. B lymphocytes transferred to normal recipients recirculated from blood to lymph. The first appearance of intravenously injected B lymphocytes in the thoracic duct was delayed relative to lymphocytes from normal donors and there was no clear cut modal recirculation time. Nevertheless their recirculation over a 48 hr period after transfusion was of the same order of magnitude as that of lymphocytes from normal donors.

scholarly journals Detection of a human CFC with a high proliferative potential

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 609-612 ◽  
Author(s):  
IK McNiece ◽  
FM Stewart ◽  
DM Deacon ◽  
DS Temeles ◽  
KM Zsebo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Growth Period ◽  
Proliferative Potential ◽  
Cell Type ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract Colony forming cells (CFC) with high proliferative potential have been detected in nutrient agar cultures of human bone marrow cells containing recombinant human interleukin-3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF). These CFC were detected by the formation of large colonies with diameters greater than 0.5 mm and containing approximately 50,000 cells after 28 days incubation. The incidence of these CFC was only two in 100,000 normal bone marrow cells; however, bone marrow from patients treated with 5-fluorouracil contained up to sevenfold higher numbers of these CFC. The characteristics of these CFC, multifactor-responsive progenitors with high proliferative potential, requiring a prolonged growth period in culture and showing a relative preservation in marrow from individuals pretreated with 5-fluorouracil, are consistent with a human cell type equivalent to the primitive murine progenitor termed HPP-CFC.

Chromosome breaks and fragile sites in leukemic bone marrow cells

1988 ◽  
Vol 33 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Kelly A. Przylepa ◽  
Sharon L. Wenger
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Fragile Sites ◽  
Chromosome Breaks ◽  
Marrow Cells

scholarly journals Evidence for the clonal abortion theory of B-lymphocyte tolerance.

1975 ◽  
Vol 141 (4) ◽  
pp. 904-917 ◽  
Author(s):  
G J Nossal ◽  
B L Pike
Keyword(s):  
Bone Marrow ◽  
Tissue Culture ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Cultured Cells ◽  
Bone Marrow Cells ◽  
Mouse Bone Marrow ◽  
Immune Competence ◽  
Self Recognition ◽  
Marrow Cells

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.

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