thesis
Microenvironments of T and B lymphocytes : a light- and electromicroscopic study
- Publication date
- 30 March 1977
- Publisher
- Peripheral blood cells- erythrocytes, granulocytes, monocytes, thrombocytes
and lymphocytes-are the end products of a differentiation process which
occurs in the bone marrow and, in rodents, also in the spleen. Normal
haemopoietic tissue is a cell renewal system with an accurate balance between
cell production originating from pluripotent haemopoietic stem cells and
continuous cell loss. The important function of haemopoietic stem cells was
emphasized by Till and McCulloch (1961) in bone marrow transplantation
studies in mice. They noted that intravenous injection of small numbers of
bone marrow cells into lethally irradiated syngeneic recipient mice caused the
appearance of haemopoietic colonies in the spleen of the recipient mice. These
colonies consisted either of erythroid, gran uloid, megakaryocytic or mixed cell
populations (Curry and Trentln, 1967). The technique used by Till and
McCulloch is known as the "spleen colony assay" and has established two
major qualities of haemopoietic stem cells: (I) they have the capacity of self
replication (Trentin and Fahlberg, 1963; Curry et a!., 1967) and (2) they are
pluripotent since they give rise to clones of different cell types of which the
differentiated "end" cells recirculate in the blood (Till and McCulloch, 1961;
Becker eta!., 1963; Till, 1976). In contrast to erythroid and myeloid colonies,
lymphoid colonies were not detectable with the spleen colony assay; however,
Ford et al. (1966), Micklem et a!. (1966), and Wu et a!. (1968) demonstrated
with chromosome marker techniques that lymphoid cells were also derived
from pluripotent haemopoietic stem cells.
One of the major questions in cell biological investigations of haemopoiesis
concerns the factors which determine the commitment and differentiation of
pluripotent haemopoietic stem cells. At present it is generally accepted that
two types of factors are involved in the regulation of haemopoiesis: (I)
microenvironmental factors (see 1.2), and (2) humoral factors (see 1.4).