Showing papers on "Bone marrow published in 1976"
Journal Article•
TL;DR: Using the in vitro colony assay, clonogenic fibroblast precursor cells (CFU-F) were detected in the bone marrow, spleen and thymus from adult mice, and the pattern of post-radiation recovery of CF U-F is similar to that of the CFU-s.
1,667 citations
TL;DR: Neutrophil maturational categories, defined by morphologic criteria, were supported by autoradiographs of marrow flashed-labeled with 3H-thymidine and diisopropylfluorophosphate-32P and correlated well with the calculation of marrow neutrophil production.
Abstract: A method has been developed for measuring neutrophil cellularity in normal human bone marrow, in which the neutrophil-erythroid ratio was determined from marrow sections and marrow normoblasts were estimated by the erythron iron turnover. Neutrophil maturational categories, defined by morphologic criteria, were supported by autoradiographs of marrow flashed-labeled with 3H-thymidine. Correction for multiple counting error was empirically derived by counting serial sections through cells of each maturational category. The normal neutrophil-erythroid ratio in 13 normal human subjects was 1.5 +/- 0.07. The mean number of normoblasts in the same subjects was estimated to be 5.07 +/- 0.84 X 10(9) cells/kg. Total marrow neutrophils (X 10(9) cells/kg) were 7.70 +/- 1.20, the postmitotic pool (metamyelocytes, bands, and segmented forms) was 5.59 +/- 0.90 and the mitotic pool (promyelocytes + myelocytes) was 2.11 +/- 0.36. Marrow neutrophil ("total") production has been determined from the number of neutrophils comprising the postmitotic marrow pool divided by their transit time Transit time was derived from the appearance in circulating neutrophils of injected 3H-thymidine. The postmitotic pool comprised 5.59 +/- 0.90 X 10(9) neutrophils/kg, and the transit time was 6.60 +/- 0.03 days. From these data marrow neutrophil production was calculated to be 0.85 X 10(9) cells/kg per day. Effective production, measured as the turnover of circulating neutrophils labeled with 3H-thymidine, was 0.87 +/- 0.13 X 10(9) cells/kg per day. This value correlated well with the calculation of marrow neutrophil production. A larger turnover of 1.62 +/- 0.46 X 10(9) cells/kg per day was obtained when diisopropylfluorophosphate-32P was used to label circulating neutrophils. Studies using isologous cells doubly labeled with 3H-thymidine and diisopropylfluorophosphate-32P demonstrated a lower recovery and shorter t1/2 of the 32P label.
505 citations
TL;DR: Direct immunofluorescence is used to demonstrate cells with intracellular IgM and no detectable surface Ig in mouse foetal liver as early as 12 d gestation, suggesting that B lymphocyte precursors synthesise IgM several days before they incorporate these molecules into their plasma membranes as cell-surface receptors for antigen.
Abstract: IN BALB/c mice, surface immunoglobulin (Ig)-bearing B lymphocytes are first detectable by immunofluorescence at 17 d gestation in the liver and spleen1. Explants of 14-d foetal liver1 and spleen2, and 15-d bone marrow (our unpublished observations), have been shown to generate Ig-bearing B cells in vitro after 4–7 d of culture, suggesting that B lymphocytes normally develop multifocally in the haemopoietic tissues of mice. We have used direct immunofluorescence to demonstrate cells with intracellular IgM and no detectable surface Ig in mouse foetal liver as early as 12 d gestation. Our results suggest that B lymphocyte precursors synthesise IgM several days before they incorporate these molecules into their plasma membranes as cell-surface receptors for antigen.
393 citations
TL;DR: Alveolar macrophages were obtained from patients who had received marrow transplants for hematologic disorders and the disappearance with time of host macrophage indicates a life-span, under the conditions, of approximately 81 days.
Abstract: Alveolar macrophages were obtained from 23 patients who had received marrow transplants for hematologic disorders. The presence of a Y body in macrophages of male origin was demonstrated by fluorescence microscopy. In those patients with a marrow donor of opposite sex the alveolar macrophages were shown to be of donor origin. The disappearance with time of host macrophages indicates a life-span, under the conditions, of approximately 81 days.
359 citations
TL;DR: Findings imply a role for extracellular collagenous matrix in cell differentiation in rat diaphyseal bone formation and the onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme.
Abstract: Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation.
340 citations
TL;DR: The stroma and vascular sinuses are described by scanning and transmission electron microscopy and in freeze‐fracture etch replicas in normal rat femoral marrow and in rats made eosinophilic by larvae of trichinella spiralis.
Abstract: The bone marrow contains branching vascular sinuses lying in a fibroblastic stroma which supports hematopoiesis. This paper describes the stroma and vascular sinuses by scanning and transmission electron microscopy and in freeze-fracture etch replicas in normal fat femoral marrow and in rats made eosinophilic by larvae of trichinella spiralis. The stroma consists primarily of reticular cells which ensheath sinuses as adventitial cells and branch into the surrounding hematopoietic space. They form a spongework on which hematopoietic cells are arranged. Erythroblasts, clustered into islets, and megakaryocytes lie just outside sinuses. Granulocytes, until the metamyelocyte stage, lie in the midst of the hematopoietic cords. Lymphocytes, monocytes and likely stem cells, are clustered about arterial vessels. Macrophages occur throughout the marrow. Fat cells occur adventitial to vascular sinuses and appear to be reticular cells which accumulate fat. Processes of reticular cells closely envelope hematopoietic cells or protrude into them. Reticular cells contain rough ER and are likely fibroblastic. The argyrophilic reticular fibers of the marrow are, however, slender and scanty. Reticular cells are rich in filaments and they may contain many microtubules. They are not phagocytic and possess few lysosomes. The reticular cell cover of a vascular sinus is lifted away as maturing hematopoietic cells approach the sinus, preparatory to crossing the endothelium and entering the circulation. Maturing granulocytes often show microvilli on reaching the basal endothelial surface. The level of eosinophils in the marrow may increase from approximately four to more than 20% after injection of trichinella larvae. Close distinctive association of reticular cells and eosinophils are marked. Reticular cells provide a physical spongwork on which hematopoietic cells are supported. But I postulate that they also trap and induce differentiation of hematopoietic stem cells, and sort the differentiating hematopoietic cells into characteristic locations in their spongework.
300 citations
TL;DR: A quantitative Abelson murine leukemia virus (A- MuLV) lymphoid cell transformation assay has been developed using a semisolid agarose culture system and allows study of A-MuLV-lymphoid cell interaction at the level of single cell-single virus particle interaction.
Abstract: A quantitative Abelson murine leukemia virus (A-MuLV) lymphoid cell transformation assay has been developed using a semisolid agarose culture system. Under these conditions lymphoid cell transformation was shown to vary linearly with the dose of A-MuLV used. The susceptibility of bone marrow cells from different strains of mice to A-MuLV-induced transformation can be estimated using the agarose assay. Strains with bone marrow cells of high, medium, and low susceptibility to A-MuLV can be identified. The assay has been used to study the susceptibility of cells from lymphoid organs of fetal and adult mice to A-MuLV. Cell suspensions from fetal liver, adult bone marrow, and adult spleen are susceptible to A-MuLV, while thymocytes are resistant to A-MuLV-induced transformation. Bovine serum albumin gradient fractionation of bone marrow cells before infection with A-MuLV demonstrates that the majority of A-MuLV-sensitive cells are recovered in a broad band partially overlapping the majority of the nucleated cells. The agarose assay system allows study of A-MuLV-lymphoid cell interaction at the level of single cell-single virus particle interaction.
271 citations
TL;DR: The high frequency of this syndrome and the success in its control suggest that a controlled trial of prophylactic CNS therapy be instituted in patients with these histologic types of non-Hodgkin's lymphomas.
228 citations
Patent•
23 Jul 1976
TL;DR: In this article, a stylet is used to prevent the collection of blood and skin tissue and adjustable guard means on the tube for predetermining and limiting the depth of entry.
Abstract: The device is comprised of a guide tube having an inner end cutting edge and during insertion, carries a stylet to prevent the collection of blood and skin tissue. Adjustable guard means are on the tube for predetermining and limiting the depth of entry. After the tube has been inserted to the proper depth, the stylet is removed and a hollow needle is inserted through the tube and the bone structure into the marrow cavity to obtain a marrow sample. There are means on the needle to provide for the predetermined and limited depth of entry of the needle and motor means are provided to rotate the needle to cut through the bone and enter the marrow cavity to obtain a marrow sample. In addition after the needle has been removed, the guide tube is adapted to penetrate the bone and be moved into the marrow cavity, at which time aspiration means are connected to the outer end of the tube to aspirate marrow into the aspiration means.
210 citations
TL;DR: It is suggested that some cases of aplastic anemia may be due to an immunologically based suppression of marrow cell differentiation rather than to a defect in stem cells or their necessary inductive environment.
Abstract: Bone marrow from a patient with aplastic anemia was shown by multiple criteria to have a block in early myeloid differentiation. This block was overcome in vitro by elimination of marrow lymphocytes. Furthermore, this differentiation block was transferred in vitro to normal marrow by coculturing with the patient's marrow. We suggest that some cases of aplastic anemia may be due to an immunologically based suppression of marrow cell differentiation rather than to a defect in stem cells or their necessary inductive environment.
208 citations
TL;DR: Electron microscopy has shown that the epithelial cells from the adherent layer form a layer covering some of the attached cells in these areas and thus may provide the necessary in vitro microenvironment for granulopoiesis to occur.
TL;DR: This chapter focuses on methods for the study ofgranulocytic systems and describes both short-term cultures for the assay of granulocyte precursor cells and long-term liquid cultures forThe maintenance of stem cells.
Abstract: Publisher Summary In the last decade, several clonal techniques have been developed for studying hemopoietic cells in vitro. It was reported that mouse bone marrow cells would form colonies of granulocytes and macrophages when plated in a soft gel medium, provided a suitable source of colony-stimulating factor was present. These granulocyte colony-forming cells (or CFU,) have since been detected in a variety of species, including man. More recently, it has been shown that under suitable conditions and using appropriate stimulating factors, erythroid, megakaryocytic, T-lymphocyte, and B-lymphocyte colony formation occurs under in vitro conditions. From such cultures, a great deal of useful information has accumulated on the nature of the colony-forming cells and the characteristics of the stimulating factors. This chapter focuses on methods for the study of granulocytic systems and describes both short-term cultures for the assay of granulocyte precursor cells and long-term liquid cultures for the maintenance of stem cells.
TL;DR: The development of megakaryocyte colonies with extensive platelet production in plasma cultures seeded with mouse bone marrow cells and containing either sheep or human erythropoietin in the medium is reported.
Abstract: COLONY culture methods utilising semi-solid media which facilitate extensive cellular differentiation in vitro have proved invaluable for the quantitative investigation of granulocytic and erythrocytic progenitors and the effector substances to which they respond1,2. Colonies of megakaryocytes have been produced from suspensions of mouse bone marrow or spleen cells in agar containing lymphocyte-conditioned medium3. But these megakaryocytes did not reach the stage of maturation at which significant platelet production could be demonstrated. We now report the development of megakaryocyte colonies with extensive platelet production in plasma cultures seeded with mouse bone marrow cells and containing either sheep or human erythropoietin in the medium. The proportional relation observed between the number of colonies produced and the number of bone marrow cells plated also provides the basis of a quantitative assay method for megakaryocyte progenitors in murine haemopoietic tissues.
TL;DR: There is evidence from cytogenetic studies that stem cells differentiating into lymphocytes differ from the so-called pluripotent cells which give rise to myeloid cell lines.
Abstract: Publisher Summary This chapter deals with ultrastructural and cytochemical studies of human normal hemic cells, excluding a detailed analysis of pathological maturation. However, two types of abnormalities involving specific organelles of maturing cells are described (mitochondria with iron accumulation in erythroblasts, and crystalline granules in some leukemic granulocytes). Most of the maturation steps of immunocytes take place outside the bone marrow, that is, in the thymus and in other lymphoid tissues, and very few data are available that can distinguish on an ultrastructural basis between marrow lymphocytes and others. Furthermore, there is evidence from cytogenetic studies that stem cells differentiating into lymphocytes differ from the so-called pluripotent cells which give rise to myeloid cell lines. Numerous studies have been developed for the detection of enzymatic activities in monocytes operating in the process of intracellular digestion that follows endocytosis. At the light microscope level many reactions are available, some of which may be used as specific markers for cell line. At the ultrastructural level, cytochemical studies have established that enzymatic activities are segregated in the endoplasmic reticulum and the golgi complex, and stored into granules. With available techniques, peroxidase and some hydrolases can be detected.
TL;DR: These studies indicate that only an exceedingly small number (less than 100) of prothymocytes are required to repopulate the thymus of an irradiated mouse and this restricted number of progenitors must produce the entire repertory of T-cell immunologic responsiveness seen in the first weeks after repopulation.
Abstract: A quantitative assay for the hematopoietic precursor of thymocytes has been developed. Using this assay the kinetics of appearance of the progeny of transfused bone marrow and spleen cells in the thymus of irradiated (760 R) mice has been studied. Precursor cells are seven to eightfold more common in bone marrow than in spleen and are absent from peripheral lymph nodes. They decline in number as the animals age. When hematopoietic cells are injected immediately after lethal irradiation only a small number of cells actually enter the gland. Their progeny are not detectable in the thymus for 8-12 days. The time of their detection depends both upon the size of the residual endogenous thymocyte population and the number of progenitor cells injected. Evidence has been presented that excludes thymic injury as the basis for the delay in the appearance of donor type cells and indicates that neither the production of a "homing" signal in the irradiated animal nor the development of precursor cells are limiting factors in the rate of thymic repopulation. These studies indicate that only an exceedingly small number (less than 100) of prothymocytes are required to repopulate the thymus of an irradiated mouse. This restricted number of progenitors must produce the entire repertory of T-cell immunologic responsiveness seen in the first weeks after repopulation.
TL;DR: A plasma culture system has been used successfully to grow and quanti-tate megakaryocyte colonies from mouse bone marrow following their staining for acetylcholinesterase activity in situ.
Abstract: SummaryA plasma culture system has been used successfully to grow and quanti-tate megakaryocyte colonies from mouse bone marrow following their staining for acetylcholinesterase activity in situ. Colonies averaging about six acetylcholinester-ase-positive cells appear with a peak incidence after 4 days in culture with a plating efficiency of one colony formed for every 104 nucleated cells plated.
TL;DR: Under in vitro conditions not only mature macrophages but also nonadherent precursor cells were successfully activated and cytotoxic effects are demonstrable even at a killer target ratio of 0.5: 1.
Abstract: The capacity of bone marrow-derived macrophages to be rendered cytotoxic by macrophage cytotoxicity factor (MCF) at different stages of maturation was tested. Under in vitro conditions not only mature macrophages but also nonadherent precursor cells were successfully activated. Mature adherent bone marrow macrophages can be rendered cytotoxic for up to three weeks in tissue culture. Cytotoxic effects are demonstrable even at a killer target ratio of 0.5:1. Granulocytes do not respond to activation with MCF. Bone marrow-derived macrophages can be collected at early stages of maturation, when they grow in suspension or have developed only loose adherence. Macrophages which have differentiated in vitro from bone marrow never show any signs of nonspecific activation as measured by our cytotoxic assay system.
TL;DR: The results suggest that stem cells of adult mouse bone marrow are capable of undergoing, at most, between 80 and 200 mitoses, which is very possibly innate and the possibility that it is an artifact of the serial transfer system cannot be entirely ruled out.
Abstract: Two bone marrow cell populations, separately identifiable by means of chromosome markers, were serially transferred at 8-10 week intervals through lethally irradiated syngeneic recipients. This system allowed a precise comparison of populations derived from young and old donors; no consistent differences were observed. Both donor populations ceased to replicate after 4-5 transfers. Although more than 10(3) spleen colony-forming units were transferred, the number of colones proliferating in the bone marrow fell sharply between the second and third transfer-generations. Regenerating host cells accounted for an increasing proportion of the miroses scord in the third and subsequent transfer generations. It is concluded that many of the stem cells of bone marrow subjected to two or more transfers have decreased powers of self renewal. The results suggest that stem cells of adult mouse bone marrow are capable of undergoing, at most, between 80 and 200 mitoses. This limitation is very possibly innate, but the possibility that it is an artifact of the serial transfer system cannot be entirely ruled out.
TL;DR: The clinical findings of bone marrow necrosis in 13 patients undergoing bone marrow examination to investigate a peripheral blood cytopenia or leukoerythroblastic blood smear were reviewed and compared to those in the literature.
TL;DR: The results strongly suggest that the T cell is responsible for the induction of EAE although both the T and B cells are competent to respond to BP.
Abstract: Although both the T and B cells of the Lewis rat have immunoglobulin receptors for basic protein (BP) of myelin, and both cell types are required for antibody production to BP, the present results demonstrate that the T cells are the only cells required for the induction of experimental allergic encephalomyelitis (EAE). Both EAE and anti-BP were readily induced in thymectomized, irradiated Lewis rats reconstituted with normal thymus and bone marrow cells and challenged with BP in complete Freund's adjuvant. If the thymus cells were first treated with BP heavily labeled with 125I so as to eliminate (sucide) specific T cells, the recipients neither develop EAE nor produce antibody to BP. On the other hand, if the thymus cells were untreated and the specific B cells of bone marrow were eliminated by treatment with 125I-BP, EAE was not inhibited, although no antibody was produced. These results strongly suggest that the T cell is responsible for the induction of EAE although both the T and B cells are competent to respond to BP. Evidence was presented which suggests that neither suppressor T cells nor circulating antibody are involved in the inhibition of EAE by injection of Lewis rats with nonencephalitogenic preparations of BP. The immune status of T and B cells of the Lewis rat to BP was compared with the immune status of these cells in other species to thyroglobulin, where only the B cells appear to be competent. In this context, Brown Norway rats, which are resistant to the induction of EAE, also appear to lack T cells reactive to BP, although competent B cells are present.
TL;DR: Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains, which may eventually prove useful in clinical organ transplantation.
Abstract: Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2d and H-2b, respectively). Infusion of 10(7) (C57BL/Ka x Balb/c)F1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation.
TL;DR: The results suggest that the ability for gamma chain synthesis in erythroid cells is determined at or above the level of the precursor cell from which the erystroid colonies, in vitro, derive (probably an erythropoietin responsive stem cell), and that stimulation of fetal hemoglobin synthesis in adult erythyroid cells are possible.
Abstract: The regulation of fetal hemoglobin in adult erythroid cells was investigated with bone marrow cultures. Fetal hemoglobin (Hb F) was identified in individual erythroid colonies with fluorescent antibodies against Hb F and synthesis of gamma chains was determined with analyses of radioactive globins. The appearance of fetal hemoglobin in erythroid colonies was clonal. All the cells of the Hb F synthesizing colonies contained fetal hemoglobin. The frequency of erythroid colonies showing Hb F was higher than expected compared to the frequency of Hb F containing cells in the blood. Production of Hb F in culture, as shown by analysis of the radioactive globins, was 5 to 14 times higher than baseline Hb F synthesis. These results suggest that the ability for gamma chain synthesis in erythroid cells is determined at or above the level of the precursor cell from which the erythroid colonies, in vitro, derive (probably an erythropoietin responsive stem cell), and that stimulation of fetal hemoglobin synthesis in adult erythroid cells is possible.
TL;DR: Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal and the lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human.
Abstract: We have produced severe vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions. Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal. Gross visual impairment appeared in five of the monkeys between 33 and 45 months after the institution of the vitamin B12 deficient diet. Subsequently, in three of the visually impaired animals, a gradually progressive spastic paralysis of their hind limbs developed. Autopsies of six deficient animals showed degeneration of the peripheral visual pathway in all and of white matter in the spinal cord in four. Degeneration of several cranial nerve roots was found in four monkeys and a mild diffuse degeneration of cerebral white matter in four. The lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human. No abnormalities were found in one B12 supplemented control animal.
TL;DR: Macrophages contribute at several stages to the genesis of specific immunity leading to antibody production and cell-mediated immunity directed against specific antigens (see below), and act with nonspecific opsonins and recognition factors by exerting an antibacterial action which is not specific in the strict immuno logical sense but has a high degree of selectivity.
Abstract: In the past many different names were given to cells which we now realize are all macrophages. This came about because of the different appearances macrophages manifest when carrying out their diverse functions in different locations. Evidence that the immediate precursor of the macrophage is a blood monocyte, derived from radiosensitive cells in the bone marrow, is now overwhelming. When appropriately stimulated, macrophages are capable of active multiplication and mitotic figures are commonly seen in mononuclear phagocytes in granulomas, at sites of inflammation, and in the reticuloendothelial (RE) system and the peritoneal cavity following systemic or local treatment with a number of bacterial products (I). Consequently the number of macrophages in the body can be increased both by division as differentiated macrophages and by stimulating the output of monocytes from the bone marrow. Macrophages together with polymorphonuclear leukocytes constitute the first line of defense of the body against most infections, and specific immunity requiring Band T-Iymphocytes in general comes into play as a back-up mechanism and for long-term protection. The term "cell-mediated immunity" was originally coined to describe protection provided by macrophages, and its extension to specific immune processes, in which lymphocytes are the effector cells, is of relatively recent origin. The idea that macrophages are involved in the rejection of allogeneic cells injected into the peritoneal cavity was advanced more than 20 years ago (2), and their role in the homograft reaction has been investigated extensively (3-6). Macrophages contribute at several stages to the genesis of specific immunity leading to antibody production and cell-mediated immunity directed against specific antigens (see below). In addition they act with nonspecific opsonins and recognition factors by exerting an antibacterial action which is not specific in the strict immuno logical sense but has a high degree of selectivity. The recognition by the RE system
TL;DR: Erythropoiesis during bone marrow recovery appears to be associated with an accelerated, albeit partial, recapitulation of ontogeny.
TL;DR: It is found that an elimination after induction with the thymic polypeptide removes a substantial amount of terminal transferase from the bone marrow cell population, suggesting that at least one-half of the marrow cells bearing this enzyme are related to those found in theThymus.
Abstract: Terminal deoxynucleotidyl transferase is an enzyme which has the unique property of polymerizing polydeoxynucleotides onto a primer in the absence of a template (1,2). This enzyme is found both in the thymus and the bone marrow of birds, rodents, and humans (3-7). Whether the marrow cells that contain terminal transferase are related to thymocytes, or are on a separate pathway of differentiation, is not yet known (7,8). To determine the lineage of the murine bone marrow cells that have terminal transferase, we have investigated whether these cells have the antigen Thy-1 induced on the cells by treatment with thymopoietin (9). Thymopoietin is known to induce a set of characteristic T-cell markers including the Thy-1 alloantigen on the surface of a subpopulation of bone marrow cells committed to T-cell differentiation (prothymocytes) (10). Destruction of Thy- 1-positive cells after exposure to thymopoietin allows elimination of a substantial fraction of those bone marrow cells that can repopulate an irradiated thymus (11). We find that such an elimination after induction with the thymic polypeptide removes a substantial amount of terminal transferase from the bone marrow cell population, suggesting that at least one-half of the marrow cells bearing this enzyme are related to those found in the thymus.
Journal Article•
TL;DR: In this paper, lymphoid cells of female thymectomized and irradiated (Tx-X) PVG/c strain rats were found to be lymphopenic and had reduced numbers of cells within spleen and cervical lymph nodes.
Abstract: Qualititive, quantitative and functional differences were found in lymphoid cells of female thymectomized and irradiated (Tx-X) PVG/c strain rats as compared to normal females of the same strain. Tx-X rats were lymphopenic and had reduced numbers of cells within spleen and cervical lymph nodes, depressed transformation responses of peripheral blood lymphocytes to PHA and lower percentage killing of their spleen cells by anti-T-cell serum and complement. There was an increased percentage of immunoglobulin-bearing cells in the lymph nodes. Reconstitution of Tx-X rats by the intravenous route using syngeneic lymph node cells, spleen cells or thymocytes abrogated the autoimmune responses to thyroid components generally observed in this state. Lymph node and spleen cells, but not thymocytes, also prevented thyroid changes when given intraperitoneally. In contrast, bone marrow cells appeared to give enhanced responses. Quntitative studies showed that the relative proportions of the suppressor or autoregulatory cells in various lymphoid tissues were lymph node greater than spleen greater than thymus. Complete abrogation of the autoimmune responses was possible only when cells were administered within a short time of final dose of irradiation and moderate thyroid change was again seen if transfer was delayed for 14 days post-irradiation. At 28 days reconstitution had no influence on the development of the autoimmune responses. Preliminary characterization studies using an anti-T-cell serum and fractionation of lymph node cells on a linear Ficoll gradient suggested that autoregulatory cell is a large T cell.
Journal Article•
TL;DR: Maximal inhibition of LPS-induced differentiation was associated with increased cellular proliferation as measured by incorporation of 3H-thymidine, whereas treatment with anti-mu alone over a wide dosage range did not stimulate cellular proliferation.
Abstract: Lipopolysaccharide-(LPS) induced differentiation of mouse B lymphocytes to cells synthesizing large amounts of cytoplasmic IgM and IgG2 could be suppressed by antibodies to mu-chains. Maximal inhibition of LPS-induced differentiation was associated with increased cellular proliferation as measured by incorporation of 3H-thymidine, whereas treatment with anti-mu alone over a wide dosage range did not stimulate cellular proliferation. Spleen cells from newborn mice were suppressed by concentrations of anti-mu several hundred-fold lower than required for adult spleen cells; the adult pattern of susceptibility to suppression was acquired by 1 week of age. No significant differences in susceptibility to anti-mu were found in comparisons of adult spleen, lymph node, bone marrow, and Peyer's patch lymphocytes.
TL;DR: Induction of early lymphocyte differentiation was studied in vitro in fractionated bone marrow cells of newly hatched chickens with alloantiserums to identify newly differentiated B cells (Bu-1+) and T cells (Th-1+).
Abstract: Induction of early lymphocyte differentiation was studied in vitro in fractionated bone marrow cells of newly hatched chickens, with alloantiserums to identify newly differentiated B cells (Bu-1+) and T cells (Th-1+). Thymus extract induced selective T cell differentiation; the activity of the extract corresponds to that of thymopoietin. Bursal extract induced both B cell and T cell differentiation, but at lower concentrations B cell differentiation was always greater. This activity is ascribed to a lymphocyte-differentiating hormone of the bursa of Fabricius, for which the name bursopoietin is suggested.