Capacity Of Bone Marrow Cells Research Articles

Immunodeficiency of the Thymus-Dependent System of the Ames Dwarf Mouse

Abstract The autosomal recessive pituitary Ames dwarf mouse was immunodeficient as shown by lymphocyte depletion and involution of thymus and peripheral lymphoid tissue, lymphopenia and a wasting syndrome with subsequent death at a young age. The appearance of 19S and 7S hemolytic plaque-forming cells after immunogenic stimulation with sheep erythrocytes was delayed and considerably less in Ames dwarf mice than in normal littermates. The graft-vs-host reactivity of spleen cells, measured by the Simonsen splenomegaly assay in young (Ames × AKR)F1 hybrid mice, was significantly lower in Ames dwarf mice. On the other hand, the Ames dwarf mouse did not have marked deficiencies in the serum levels of immunoglobulin. The normal colony-forming capacity of bone marrow cells measured with the spleencolony assay of Till and McCulloch (see Ref. 13), suggested a normal stem cell population in the bone marrow of Ames dwarf mice. The earliest degenerative change of the thymus of the Ames dwarf mouse was a depletion of thymocytes from the thymus cortex frequently accompanied by an increased number of lymphoid cells in the medulla. This was followed by a loss of lymphoid cellularity of the medulla, thereby causing a complete involution of the thymus. These results suggest that the Ames dwarf mouse has an immunodeficiency of the thymus-dependent lymphoid system as a consequence of defective thymotropic influences by the pituitary.

Influence of neonatal thymectomy on cloning capacity of bone marrow cells in mice.

ALTHOUGH the bone marrow cell population is known to affect both the structure and function of thymus tissue1, experimental data indicating any defined influence of the thymus on bone marrow anatomy or physiology are scanty and inconclusive2. Thymectomy performed in Wistar rats a few weeks after birth does not modify their bone marrow cell population3. Thymectomy within 48 h of birth seems to produce an increase in the number of blasts (stem cells) and immature erythroblasts normally present in this tissue, however4. An increased percentage of immature erythroblasts in the bone marrow of thymectomized embryos has also been described in the opossum5.

The influence of continuous irradiation on the colony-forming activity of mouse bone-marrow.

Injected stem cells of the bone-marrow of mice form colonies of haematopoietic tissue in the spleen of an irradiated host and this can be used to obtain stem-cell survival curves after irradiation in vivo or in vitro (Till and McCulloch 1961). The repopulation capacity of bone-marrow cells after fractionated irradiation has been studied, too (Porteous and Lajtha 1966). This paper reports changes in the count of stem cells in the bone-marrow of mice after continuous irradiation by gamma-rays at a low dose-rate. Both male and female C57B mice were used; at the start of irradiation they were 12 weeks old. The irradiation was applied continuously for 24 hours a day and was interrupted every other day for about 10 min to replenish food and clean the cages. The animals were placed into the irradiated space at various intervals so as to obtain groups given accumulated doses of from 40 to several hundred R. All animals used for a given series of experiments stemmed from the same group of the same age. For each series the stem-cell counts of irradiated mice were compared with non-irradiated controls. These controls were kept throughout the irradiation in the same space, but their exposure was prevented by concrete shields of proper dimensions. Thus the controls could not receive doses larger than 2 mR/day. So far, three different dose-rates have been tested-24-0 R, 8-0 R and 27 R per 24 hours. The mice were killed after the irradiation was completed, and a suspension of cells in Hanks' solution was prepared from the bone-marrow of tibiae and femurs. This suspension was injected into host animals of the same strain in doses of 105 nucleated elements per mouse. Host mice were irradiated by a dose of 650 R twenty hours before injection. By the 10th day after injection the mice were killed, and colonies of the haematopoietic tissue at the facies parietalis of the spleen were counted. The individual points in the plots are the mean values estimated for groups consisting of 12-15 mice. The background value, 0-3-0-6 colony per mouse, was subtracted. The results show that the count of stem cells in the bone-marrow responds to continuous irradiation by a decrease at all three dose-rates (figure). The initial decrease is the same at 24 R and 8 R per day, whereas a somewhat lower decrease was brought about by the same dose accumulated at a daily rate of 2-7 R, the difference, however, being not statistically significant. Accumulated doses larger than 200 R were tested only at daily rates of 24 R and 2-7 R. The difference between both plots is considerable. With several groups there has been observed at 27 R/day a recovery to normal values followed by another decrease, and this course recurred. As this experiment is rather timeconsuming at a rate of 27 R/day, it was carried out only twice. The same results could be obtained also for the second run, i.e. an alternating decrease to R.B.

Dependence of bone marrow cells on the liver for purine supply.

IT is well known that higher organisms can utilize the carbon atom of formate molecules for the synthesis of purines, as indeed can liver tissue in vitro. However, in rabbit and human bone marrows and in Ehrlich ascites cells of the mouse, formate-14C was found to be utilized very inefficiently for de novo synthesis of purines in vitro, but very efficiently for labelling thymine in deoxyribonucleic acid1–3. As liver extracts restore the ability of these cells to synthesize purines in vitro 4, it was suggested that, in vivo, the capacity of bone marrow cells for synthesis of purines may be so limited that they depend on the liver for the supply of purines. This inference was tested experimentally by measuring the amount of formate-14C incorporated into the deoxyribonucleic acid bases of bone marrow cells in control and hepatectomized rabbits.