Biomedical Engineering Reference
In-Depth Information
Pluripotent HSC
Myeloid Stem Cell
Lymphoid Stem Cell
Platelets
Basophil
Progenitor
Granulocyte-Monocyte
Progenitor
Erythrocytes
T cell
B cell
NK cell
Basophil
Mast Cell
Eosinophil
Monocyte
Neutrophil
Dendritic Cells
Macrophage
FIGURE 6.1
Basic hematopoietic schematic. Pluripotent hematopoietic stem cells (HSC)
give rise to myeloid and lymphoid lineages. Myeloid stem cells differentiate to form eryth-
rocytes, platelets, basophils, mast cells, eosinophils, monocytes, neutrophils, and myeloid
dendritic cells. The lymphoid lineage gives rise to lymphoid dendritic cells, NK cells, and B
and T cells whose development is discussed in detail in
Chapter 7
.
fore, the core constituents of the innate immune response. There is strong evidence
that NF-
B plays a prosurvival role during the development of dendritic cells and
NK cells and is also involved in granulopoiesis.
As mentioned above, I
κ
knockouts display markedly abnormal nonlymphoid
hematopoiesis. These mice are characterized by inflammatory infiltrates at multiple
sites and exhibit robust granulocytosis [1]; however, the nature of the alteration in
granulopoiesis has not been clearly defined. The most specific effect of I
κ
B
α
B knock-
outs has been observed in NK cell development. Chimeras made with cells from
i
κ
-/-
mice show a moderate defect in both myelopoiesis and granulopoiesis
[15]. More strikingly, cells from these mice have a pronounced alteration in NK
development
in vivo
, consistent with the severe defect in development of lymphoid
lineages [16]. Unexpectedly, the elevated levels of NF-
κ
b
α
-/-
i
κ
b
ε
B activity in these cells is
believed to exert a proapoptotic effect, a concept that will be discussed more exten-
sively in the context of lymphopoiesis (Chapter 7).
Aspects of dendritic cell (DC) development are also dependent on NF-
κ
B.
Although knockouts of c-Rel, p50, and p65 do not have obvious effects, loss of
RelB results in a striking defect in the development of DCs [17,18]. Dendritic cells
may be of myeloid or lymphoid origin, with the latter being further divided into
multiple subtypes, the most common distinction in mice being made on the basis
of differential CD8
κ
α
expression. RelB is specifically required in the development
of CD8
+
, DCs [19]. Conversely, classical p50/p65 complexes are
required for the development of both CD8
α
-
, but not CD8
α
-
dendritic cells, despite
normal development of other myeloid and lymphoid lineages under the same con-
α
+
and CD8
α
