Hematopoiesis, Including Lymphocyte Development and Maturation

Hematopoiesis, including lymphocyte
development and maturation

A1
Valerie F.J. Quesniaux, Julian D. Down, Henk-Jan Schuurman
characteristic of the competent immune system, and

Introduction: acquisition of specificity is only touched upon in describing affinity matura-
tion of matured B cells. Most of the knowledge
The immune system has some unique properties described in this chapter is based on studies in mice;
which distinguish it from other homeostatic systems although there are many differences between
in the body. First, it shows an extreme specificity and rodents and humans in the complex structure and
discrimination in recognition of ‘self’ and ‘nonself’ function of the immune system [1], T and B LYMPHO-
ANTIGENS of potentially pathogenic microorganisms CYTE maturation in other species relevant for the dis-
or substances in the external environment.Second,it cipline of immunopharmacology (rat, man) follows
carries ‘memory’, resulting in a more rapid and avid similar principles.
response to ANTIGENS upon secondary contact.Third,
it responds to antigen in multiple ways, resulting in a
variety of potential mechanisms to inactivate or Hematopoiesis
destruct its targets. Related to this, there is a finely-
tuned regulatory network of cells and their products A diagram of HEMATOPOIESIS [2] is presented in Fig-
maintaining homeostasis in the system or dampen- ure 1. It starts with the pluripotent hematopoietic
ing reactions when imbalances arise. LYMPHOCYTES STEM CELL. While blood cells in the embryo may first
have a central function; for instance, specificity is a be derived from hematopoietic cells residing in the
characteristic of these cells. This chapter describes yolk sac; current evidence strongly suggests that the
their development and maturation, up until the stage AORTA-GONAD-MESONEPHROS region is the source of
at which the cells are able to exert their function in the definitive adult hematopoietic system,which sub-
host defence. Development and maturation of lym- sequently colonizes the liver and then the BONE MAR-
phoid cells is part of the production of blood cells ROW [3]. In adults, hematopoietic STEM CELLs occur
called HEMATOPOIESIS. HEMATOPOIESIS includes the for- almost uniquely in the BONE MARROW; only a very
mation of ERYTHROCYTES (red blood cells), THROMBO- small subset of hematopoietic cells in the peripheral
CYTES (platelets), and LEUKOCYTES (WBC, white blood circulation has STEM CELL potential. In rodents,
cells) in blood; white blood cells can be differentiat- extramedullary hematopoietic activity can also be
ed into POLYMORPHONUCLEAR neutrophilic GRANULO- observed in the red pulp of the spleen.Hematopoiet-
CYTES, eosinophilic GRANULOCYTES and basophilic ic STEM CELLs are self-renewing and produce a contin-
GRANULOCYTES, MONOCYTES, and LYMPHOCYTES. In uous supply of mature cells for the whole life-span.
organs, including LYMPHOID ORGANS, the products of The progeny of the pluripotent hematopoietic STEM
hematopoiesis are DENDRITIC CELLS, MACROPHAGES (his- CELL comprises cells committed to different lineages
tiocytes) and mast cells. Although the focus of this in the hematopoietic system; a first differentiation
chapter is on the lymphoid lineage, some aspects of involves the production of myeloid and lymphoid
hematopoiesis will be described as well. Within the committed progenitor cells. The myeloid progenitor
lymphoid lineage, the focus is on the acquisition of subsequently gives rise to precursors of erythrocytes,
specificity, because this is the major event during thrombocytes, GRANULOCYTES, and MONOCYTES. These
development and maturation. Memory is a typical precursor cells can be measured in vitro in so-called
4 Hematopoiesis, including lymphocyte development and maturation
FIGURE 1 (continued on next page)

Schematic representation of hematopoiesis, starting with a pluripotent stem cell that develops in a common myeloid
progenitor cell or a common lymphoid progenitor cell, and subsequently results in the generation of all blood cell pop-
ulations: erythrocytes or red blood cells, thrombocytes or platelets, and white blood cells that include macrophages,
neutrophilic, eosinophilic and basophilic granulocytes, and mature T or B lymphocytes. The nomenclature of cells in
intermittent phases is shown, as well as the cytokines promoting various steps in the development of hematopoietic
cells in distinct lineages.

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Hematopoiesis, including lymphocyte

development and maturation

characteristic of the competent immune system, and

FIGURE 1 (continued on next page)

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