Introduction
•Leukopoiesis is the process of formation of leukocytes (white blood cells) from stem cells in haematopoietic organs.
•Leukocytes develop from either multipotential myeloid stem cells (CFU-GEMM) or multipotential lymphoid stem cells (CFU-L).
•Leukocytes developing from CFU-GEMM’s are granulocytes (neutrophils, basophils andeosinophils) or monocytes.
•Leukocytes developing from CFU-Ls are lymphocytes (T & B cells, dendritic and NK cells).
Granulopoiesis
•All granulocytes develop from the CFU-GEMM cells.
Neutrophils
•Under the stimulation of cytokines GM-CSF, G-CSF and IL-3 the CFU-GEMM differentiates into the CFU-GM, the common precursor for both neutrophils and monocytes.
•This then further differentiates into CFU-G.
Stages
•Myeloblast
•Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.
•Promyelocyte
•During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.
•Neutrophilic myelocyte
•The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.
•Neutrophilic metamyelocyte
•At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney-like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.
•Band cell
•Nucleus elongates further and represents a horseshoe. Nucleus starts to segment.
•Neutrophil
•Mature neutrophil is formed, and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
Basophils
•Under the stimulation of GM-CSF and IL-3, the CFU-GEMM differentiates into CFU-Ba.
•Stages:
•Myeloblast & Promyelocyte
•These stages are common to all granulocytes, and no distinction can be made between different cell lines.
•Basophilic myelocyte & metamyelocyte Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.
Basophil
Final nuclear shape is masked by the high density of cytoplasmic granules.
Eosinophils
•Under the stimulation of GM-CSF, IL-3 and IL-5 the CFU-GEMM differentiates into the CFU-Eon.
•Stages:
•Myeloblast & Promyelocyte
•These stages are common to all granulocytes, and no distinction can be made between different cell lines.
•Eosinophilic myelocyte & metamyelocyte
•Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
•Eosinophil
•Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
Monocytes
•Monocytes develop from the same precursor as neutrophils – the CFU-GM. This then differentiates into the CFU-M under the influence of GM-CSF, IL-3 and M-CSF.
•Stages:
•Monoblast
•This is the first stage after cell has differentiated into the CFU-M.
•Promonocyte
•Cell has a large nucleus and basophilic cytoplasm and consists of two populations: – One rapidly dividing and the other slowly dividing, which acts as a reservoir.
•Monocyte
•Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.
•Macrophage
•Once the monocyte has entered tissue it differentiates into a macrophage.
•Dendritic cells
•These develop from the monoblast under the stimulation of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature dendritic cell under stimulation of TNF-α.
Lymphopoiesis
•Lymphocytes develop from the CFU-L‘s. Those destined to become T cells leave the bone marrow and migrate to the thymus, and those destined to be B cells migrate to the spleen and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
| B cell | T cell | |||
| Differentiation | CFU-L | |||
| ▼IL-7 & IL-11 | ▼IL-7 & SCF | |||
| B lymphoid cell progenitor | T lymphoid cell progenitor | |||
| ▼IL-3 & IL-7 | ▼IL-7 | ▼IL-2, IL-12 & IL-18 | ▼IL-3, IL-6, GM-CSF & SCF | |
| Pre-B cell | Pre-T cell | Pre-NK cell | Pre-Dendritic cell | |
| Maturation site | Bone marrow, spleen or GALT Cloacal bursa (birds) | Thymus | ||
| Mature | B cell ▼(Antigen stim.) Plasma & Memory cell | T Cell Helper Cytotoxic Regulatory | NK cell | Dendritic cell |