Bone Marrow

Abstract

Bone marrow is the site of production of blood cells: granulocytes, lymphocytes, macrophages, platelets and red cells; it also plays a major role in the control of cell production.

Keywords: bone marrow; haematopoietic stem cells; growth factors; cell kinetics; bone marrow transplantation

Figure 1.

Cross‐section of mouse femoral bone marrow. CAP, capillary; EB, erythroblasts; G, granulocyte precursor; L, lymphocytes; MK, megakaryocyte. H & E; original magnification ×200.

Figure 2.

Paracrine and juxtacrine regulation of bone marrow function. GF, growth factor; N, nucleus.

Figure 3.

Haematopoiesis in mice. Long‐term repopulating haematopoietic stem cells belong to a population of cells which bears none of the markers present on mature blood cells (lineage negative) and is characterized by the following markers Thy 1.1lo, Sca1+, Kit+, Rho−/lo; about 10 percent of cells in such a population will, when injected into lethally irradiated mice, continue to produce mature multilineage progeny for at least 11 months. The turnover time of the population containing long‐term repopulating stem cells, as inferred from labelling studies with bromodeoxyuridine or the proportion of cells in S/G2/M phases of the cell cycle, is about 20 days. Short‐term repopulating stem cells belong to a population bearing, in addition to the markers indicated for long‐term repopulating stem cells, Mac‐1lo and CD4−/lo. When injected into irradiated mice, cells of this type are able to produce multilineage descendants for 8–16 weeks. The population containing short‐term stem cells has a turnover time of 5–2 days, as judged by the proportion of cells in S/G2/M, depending on whether they are CD4 or CD4lo. Common lymphocyte progenitors are Li, IL7Ra+, Thy1.1, Sca1lo*, Kit+, S+G2+M = 22%. (*Sca1lo means Sca1 fluorescence less than that of long‐term repopulating stem cells.) T, T cell; B, B cell; NK, natural killer cell; G, granulocyte; M, monocyte; E, erythrocyte; MK, megakaryocyte; Ma, macrophage.

Figure 4.

B lymphopoiesis in mice. In this figure and Figures and , kinetic analysis of [3H]TdR‐labelled cells has been carried out following the rules governing concatenated cell compartments in steady state. Compartments of cells are represented by circles. In steady state, the number of cells in each compartment is invariant and input = output. The number of cells in a compartment, n2, equals the input of cells into the compartment multiplied by either the cycle time (Tc) for proliferating cells, or the transit time (Tt) for nonproliferating cells. The input into n2 is consequently equal to either n2/Tc or n2/Tt. For proliferating compartments in which there is no cell loss the input into compartments, In2 = o1 × 2; when there is loss In2 = o1 × 2(1−Lf) where Lf = loss factor, fraction of the output which is lost and does not proceed into the next compartment. For nonproliferating compartments In2 = o1, or In2 = o1(1−Lf).

Blue triangle, B‐220 marker; purple circle, CD19 marker; Ig, immunoglobulin; H, heavy; L, light; Cμ, cytoplasmic μ chain; Y, surface IgM; TdT, terminal deoxynucleotide transferase; G, immunoglobulin genes in germline configuration; R, rearranged genes; E, early; I, intermediate.

Figure 5.

Granulocytopoiesis in humans. Cell cycle times (Tc) are estimated on the basis of published labelling indices and measured duration of S phase (11 hours as estimated from the [3H]TdR by fraction‐labelled mitosis curve analysis). It is assumed that myelocytes go through two cycles, as the cycle time of 1.4 days and the published transit time (Tt) of 2.9 days, do not agree. The input into promyelocytes is estimated to be equal to the total number of promyelocytes divided by promyelocyte Tc. Cell loss is postulated to occur in the actively dividing myelocyte and promyelocyte compartments, as there appears to be no amplification in the system. The total cell contents and transit times in the nondividing compartments show that no loss occurs in these compartments.

Figure 6.

Erythropoiesis in humans. Haemoglobin (Hb) content was measured in cells in mitosis; cycle time from [3H]TdR labelling studies. ΔHb, increase in Hb content per cell cycle; Tc, cycle time; Tt, transit time.

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Further Reading

Athens JW (1993) Granulocytes‐neutrophils. In: Lee GR, Bithell TC, Forrester J, Anthens JW and Lukens JN (eds) Wintrobes Clinical Hematology, 9th edn, vol. 1, pp. 223–226. Philadelphia: Lea and Febiger.

Jandl JG (1987) Physiology of red cells. Blood Textbook of Hematology, pp. 51–53. New York: Little, Brown.

Kondo M, Weissman GL and Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91: 661–672.

Metcalf D (1995) The granulocyte‐macrophage regulators. Experimental Hematology 23: 569–572.

Morrison SJ, Uchida N and Weissman GL (1995) The biology of hematopoietic stem cells. Annual Review of Cell and Developmental Biology 11: 35–71.

Osmond DG (1990) B cell development in bone marrow. Seminars in Immunology 2: 173–180.

Shivdasani RA and Orkin SH (1996) The transcriptional control of hematopoiesis. Blood 87: 4025–4039.

To LB, Haylock DN, Simmons RJ and Juttner CA (1997) The biology and clinical uses of blood stem cells. Blood 89: 2061–2067.

Vogelsang GB and Hess AD (1994) Graft‐versus‐host disease: new directions for a persistent problem. Blood 84: 2061–2067.

Zhong A‐K, Astle M and Harrison E (1996) Distinct developmental patterns of short term and long term functioning lymphoid and myeloid precursors defined by competitive limiting dilution analysis in vivo. Journal of Immunology 157: 138–145.

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How to Cite close
Hodgson, George S, and Dunn, Ashley R(Apr 2001) Bone Marrow. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000505]