Hematopoiesis is the production of blood cells, a developmental process located in the (red)
bone marrow, though some cells mature elsewhere. For example,
T lymphocytes are so named because they
mature in the
thymus, and
antigenic stimulation of
B lymphocytes to become
plasma cells typically takes place in the periphery.
▼
B lymphocyte development :
common lymphoid progenitor :
common myeloid progenitor :
E2A :
EBF :
early B lineage :
erythropoiesis :
granulopoiesis :
hematopoietic growth factors :
lymphopoiesis :
monocytopoiesis :
Pax-5 :
pluripotential stem cell :
precursors :
progenitors :
regulatory transcription factors :
stages :
stem cells :
thrombopoiesis :
transcriptional regulatory proteins▼
The process of haematopoiesis occurs in several
stages, and is controlled by at least 11
hematopoietic growth factors (including the
colony-stimulating factors,
IL-2 through
IL-7,
G-CSF,
GM-CSF, and
M-CSF).
The first stage involves the differentiation of a
pluripotential stem cell into a
committed progenitor, which is followed by
maturation of committed progenitors in distinct pathways, in which
precursors are partially developed, 'adolescent' cells
en route to maturity.
stem → progenitor → precursor → adult → mature
[]
labeled photomicrograph of bone marrow,
diagram of adult stem cell plasticity,
diagram of stem cell versus progenitor cellStem cell stage:
pluripotential hematopoietic stem cell
↓ --------------------↓
The common myeloid progenitor can generate:
● proerythroblasts (pronormoblasts) → erythropoiesis
● myeloblasts → granulopoiesis
● monoblasts → monocytopoiesis
● megakaryoblasts → thrombopoiesis
The common lympoid progenitor can generate:
● lymphoblasts → lymphopoiesis
Committed progenitor stage to mature cell : granulopoiesis
common myeloid progenitor
↓
myeloblast
↓
B/E/N promyelocyte
↓---↓---↓
B/E/N myelocyte
↓---↓---↓
B/E/N metamyelocyte
↓---↓---↓
B/E/N band
↓---↓---↓
basophil, eosinophil, neutrophil
↓ -----------------------
mast cell -----------------------
Committed progenitor stage to mature cell : lymphopoiesis
common lymphoid progenitor
↓
lymphoblast
----------------------------------------↓ rearrangements H: D-J → H: V-DJ
prolymphocyte
-----------------↓ rearrangements L: V-J --------------------------↓
small lymphocyte------or----- natural killer cell (large granular lymphocyte)
------------↓ IgM→IgD ---------↓------------------------------------ ↓
------B lymphocyte--or-- T lymphocyte
------------↓----------------------------------------------------------- ↓
--------plasma cell------------------------------------------lymphoid dendritic cell
Development of mature B lymphocytes from multipotent progenitors requires the coordinated activities of a number of transcriptional regulatory proteins, including EBF, Pax-5, and E2A.
During B cell-development from the precursor stage, differentiation involves rearrangement of the heavy chain gene segments. The functional integrity of the rearranged gene is tested: Precursor-B cells express two single domain Ig-like proteins of invariant sequence that substitute for the light chain. Formation of a complex comprising the μ (mu) heavy chain with the surrogate light chains instructs the cell to discontinue rearrangement of the heavy chain locus and to commence rearrangement of the k (kappa) locus. If successful light chain rearrangement is achieved such that the light and heavy chains form a complete antibody, then this complex instructs the cell to discontinue rearrangement of light chains, ensuring that only a single specificity is produced (allelic exclusion). Џ B cell maturation - animation Џ
Those developing B cell clones that fail to generate a productive rearrangement at both one of their heavy chain alleles and a light chain locus will undergo apoptosis. Immune tolerance mechanisms also exist to ensure the death of any newly produced B cells that express an antibody that reacts strongly with self proteins on the surface of host cells.
E2A proteins function in early B lineage development to regulate B lineage-specific gene expression as well as B cell survival. E2A-encoded proteins are involved in the differentiation of a number of cell types, and they are especially important in lymphocyte development.
The E2A gene encodes E47 and E12, which are basic-helix-loop-helix (bHLH) transcription factors that bind DNA either as homodimers or as heterodimers with other bHLH proteins. Such bHLH DNA binding activity in the B-lineage comprises E47 homodimers. Development of thymocytes mainly involves heterodimers of E47 and a related bHLH protein, HEB. Thymocytic E2A protein expression is required to initiate T-cell differentiation. During the development of thymoctyes, E-proteins and their antagonists, Id2 and Id3, regulate T-lineage specific gene expression and TCR rearrangement. E2A and Id proteins block thymocytic maturation in the absence of pre-TCR expression, and pre-TCR signaling acts to promote development in part by inhibiting E2A activity. [l]
Committed progenitor stage to mature cell : monocytopoiesis
common myeloid progenitor
↓
monoblast
↓
promonocyte
↓
monocyte
↓ ----↓
macrophage or myeloid dendritic cell
Committed progenitor stage to mature cell : erythropoiesis
common myeloid progenitor
↓
proerythroblast
↓
basophilic erythroblast
↓
polychromatic erythroblast
↓
polychromatic erythrocyte (reticulocyte)
↓
erythrocyte (RBC)
Committed progenitor stage to mature cell : thrombopoiesis
↓
megakaryoblast
↓
promegakaryocyte
↓
megakaryocyte
↓
thrombocytes (platelets)
tags
[Immunology] [hematopoiesis]Labels: B lymphocytes, bone marrow, hematopoeisis, plasma cells, T lymphocytes
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