Lymphoid stem cell

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

Pluripotent stem cell -----------> lymphoid stem cell---------------> lymphocytes... 

Lymphocytes are one of the primary cell types involved in the immune response. There are two general types of lymphocytes, B and T. Both are derived from bone marrow lymphoid stem cells, but T cells go through an additional maturation process in the thymus. Although the morphology of T cells and B cells is similar, the functions of these two types are distinct. After antigen exposure, B cells develop into antibody-producing plasma cells, whereas T cells are divided into functional subtypes that possess distinct cell surface antigens. 

A continuation of this line of studies for 6 days to 23 weeks at 300 ppm showed continued decreases in numbers of mature B- and T-lymphocytes produced in the bone marrow, spleen, and thymus (Rozen and Snyder 1985). Abnormalities of humoral and cell-mediated immune responses following benzene exposure are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. Bone marrow cellularity increased 3-fold, and the number of thymic T-cells increased 15-fold in benzene-exposed mice between the 6th and the 30th exposure. No corresponding increase in splenic cells was noted. The marked increase in the numbers of cells in bone marrow and thymus was interpreted by the authors to indicate a compensatory proliferation in these cell lines in response to... 

Leene, W., Duyzings, M. J. M. and VonSteeg, C. (1973). Lymphoid stem cell identification in the developing thymus and bursa of Fabricius of the chick. Z. Zellforsh 136, 521-533. 

A basic understanding of normal hematopoiesis is needed before one can understand the pathogenesis of leukemia. The reader is referred to Chap. 98 for a detailed discussion of hematopoiesis. Normal hematopoiesis consists of multiple well-orchestrated steps of cellular development. A pool of pluripotent stem cells undergoes differentiation, proliferation, and maturation, to form the mature blood cells seen in the peripheral circulation. These pluripotent stem cells initially differentiate to form two distinct stem cell pools. The myeloid stem cell gives rise to six types of blood cells (erythrocytes, platelets, monocytes, basophils, neutrophils, and eosinophils), while the lymphoid stem cell differentiates to form circulating B and T lymphocytes. Leukemia may develop at any stage and within any cell line. 

Another continuously replenished tissue is the blood, whose stem cells are located in the bone marrow in adult animals. The various types of blood cells all derive from a single type of pluripotent hematopoietic stem ceii, which gives rise to the more-restricted myeloid and lymphoid stem cells (Figure 22-5). The frequency of hematopoietic stem cells is about 1 cell per 10 bone marrow cells, even lower than the frequency of intes-... 

D. Thymosin Thymosin is a protein hormone from the thymus gland that stimulates the maturation of pre-T cells and promotes the formation of T cells from ordinary lymphoid stem cells. Thymosin-containing preparations have been used in DiGeorge s syndrome (thymic aplasia), but their efficacy in other immune deficiency states has not been established. 

Another important cell type in the innate immunity system is the natural killer (NK) cell (Figure 14.12), which is a member of a class of leukocytes called lymphocytes, because it is derived from a type of stem cell called a lymphoid stem cell. NK cells kill off cells that have been infected by viruses or... 

SCID patients, if untreated, usually die within 1 year due to severe, recurrent infections such as chronic diarrhea, ear infections, recurrent pneumonia, and profuse oral candidiasis. The ADA dehciency leads to an accumulation of purine metabolites, in particular dGTP, which are cytotoxic to lymphoid stem cells. Restoration of normal ADA levels removes the dGTP and allows the lymphoid stem cells to propagate. Pegademase is administered intravenously, stored at 4°C, and should never be frozen [77]. 

Pluripotent stem cell -Lymphoid stem cell ... 

There are many different cell types in the immune system and these cells interact in a complex reaction of signaling and communication to create the overall response. The cells of the immune system derive from two types of cells in the bone marrowy myeloid stem cells and lymphoid stem cells. Myeloid cells give rise to precursor cells of the innate immune system, whereas lymphoid cells generate precursors of cells of the adaptive immune system. Chemokine receptors are found on almost all immune cells. 

Lymphoid stem cell A cell in the bone marrow from which lymphocytes develop. 

In ADA-deficiency transplantation of bone marrow derived lymphoid stem cells is the method of choice. However, in most instances no suitable bone marrow donor is available. Enzyme replacement therapy with irradiated normal erythrocytes to lower accumulated dAdo and dGuo has resulted in some ADA- or PNP-deficient patients in improvement of immune function (4,5,6,7). Iron overload and... 

The gene for ADA has been tentatively assigned to chromosome 20 so that there is no linkage with the major histocompatibility locus, assigned to chromosome 6 in man. There is an independent assortment of HL-A haplotypes and ADA deficiency in families with infants affected with severe combined immunodeficiency. Thus, it appears likely that the ADA deficiency has a causal relationship to severe combined immunodeficiency and that lymphoidal stem cells may be particularly vulnerable to the consequences of the absent or abnormal ADA. 

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