Lymphoid cell precursors

The thymus is a lympho-epithelial organ, located within the upper thorax. One of its fimctions is the conversion of certain lymphoid hematopoietic precursor cells originating from the bone marrow into thymus-derived lymphocytes (T-cells). 

Yoneyama H, Matsuno K, Zhang Y, et al. Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 2(X)I I93(I) 35M9. 

Leucocyte All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. 

T cell development, similar to B cell ontogeny, can also be divided into stages based on antigen expression (Table 4) extrathymic precursor, prothymocyte, immature thymocyte, common thymocyte, mature thymocyte, and mature peripheral T cell. However, while the early stages of T cell development are well characterized, the later stages of T cell differentiation, that is, those of the mature peripheral T cell, have not been fully delineated (C3, F12, H13, K15, K16, K20, R6-R8,V3, V4). Furthermore, although natural killer (NK) cells are closely related to T cells (S21), the stages of differentiation of this lymphoid cell population are not completely understood. 

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... 

The utilization of peripheral blood lymphoid cells as target cells for evaluating the immunomodulatory effects of thymic factors is based on the assumption that circulating thymic hormones continue to interact with mature T cells and play a role in the maintenance of thymic-dependent immunity. Because of the ease in isolating peripheral blood lymphocytes from venipuncture specimens, this population of cells has frequently been employed experimentally. It must be emphasized, however, that when unffactionated peripheral blood lymphocytes are used as target cells, the predominant cells present are mature T lymphocytes. Thus, when unfiactionated peripheral blood lymphocytes are used as targets, it would be difficult to discern any effects on T cell precursors since they would make up, at best, only a very minor component of the lymphoid population being studied. 

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. 

In some recent studies it has been reported that 3-aminobenzamide (SAB), an inhibitor of poly(ADP-ribose) polymerase [7, 10] also inhibits the pathway for de novo synthesis of DNA precursors. Specifically, SAB inhibits the metabolism of glucose and methionine into precursors of DNA in WI-L2 lymphoid cells [6], C3H mouse fibroblasts [1], and Chinese hamster ovary (CHO) cells [4]. It has been suggested that some of the reported effects of SAB, such as its effect on cell-cycle progression [8], may be due to a disturbance in nucleotide precursor pathways rather than an inhibition of poly(ADP-ribose) synthesis [1—4, 6]. To test this hypothesis, we have examined the effects of SAB on SCE induction, cytotoxicity, and cell-cycle progression in three different human lymphoblastoid cell lines two deficient in salvage nucleotide synthesis pathways and one competent in both salvage and de novo nucleotide synthesis. We hypothesized that if SAB inhibits de novo nucleotide synthesis pathways, then cells deficient in salvage nucleotide synthesis pathways should be more sensitive to the various effects of SAB, especially its cytotoxic and cell-cycle effects. 

Hematopoietic Stem Cell Precursor cell that has the abihty to rephcate and proliferate into all the lymphoid and myeloid blood cell lines. 

Because of the rapid synthesis of DNA during differentiation, lymphoid cells would be expected to be particularly sensitive to abnormalities in the regulation of the nucleoside pools that serve as precursors for DNA synthesis. The synthesis of thymidine triphosphate is of particular interest because of its specificity for DNA synthesis. The rate limiting step in the de novo pathway to dUMP involves conversion of dUPM to a dTMP by the folate requiring enzyme thymidylate synthetase, vitro incorporation of 3H-thymidine and 3n-deoxyuridine is reduced in bone marrow cultures from folic acid deficient rats (Sakamato and Takaku, 1973). Thymidylate synthetase activity was elevated when assayed in the presence of adequate cofactor (5,10-methylene THF). A salvage pathway also exists for the direct phosphorylation of thymidine by thymidine kinase. This enzyme can exist in two forms (Ellims et al., ... 

The current hematopoietic model also proposes the existence of a lymphoid-restricted CLP, which can be separated from the CMP based on expression of the IL-7 receptor. The progeny of the CLP develop into B cell precursors that remain in the bone marrow or T cell precursors that migrate to the thymus. Although mature lymphocytes are generally quiescent, specific memory T and B cells can be reactivated by their cognate antigen to proliferate, expand, and fight infection. 

Terminal deoxynucleotidyltransferase is a group of DNA polymerases which, unlike DNA- or RNA-directed polymerases, require neither DNA or RNA templates but catalyze linear condensation polymerization reactions. Terminal deoxynucleotidyltransferase is traditionally abbreviated as TdT, However, this book will break with the tradition and use TDTase to avoid any possible confusion with the dinucleotide TdT. TDTase, which was first isolated from the calf thymus gland, is found almost exclusively in the thymuses of a wide variety of mammals and birds and in certain lymphoid cells. TDTase from calf thymus is a heterodimer (44 kDa) and both subunits are derived from a single polypeptide precursor ( 60 kDa). 

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