Figure 1 Different pathways of T and B lymphocyte.

antigens, and their phenotype can be defined as Thy-J , Ig , B220'. There are no good markers to distinguish the progenitors of B cells from pro-B cells, which are the most primitive B cells giving rise to the B lineage.

Stroma cells in fetal liver and bone marrow constitute the microenvironment in which lymphocytes of the B lineage differentiate. Stroma cells are considered to be nonhematopoietic and are a very heterogeneous population, but it is not clear whether or not stroma cell subsets have different effects on the differentiation process of various lineages. Stroma cells produce biologically active substances which can play an important role in the differentiation and proliferation processes. For example, there is good evidence that interleukin 7 (IL-7), which promotes the proliferation of pro-B cells as well as of the double negative (CD4~ CD8 ) T cells, is a product of stromal cells.

The pro-B cell (pre-B I cell) is the most primitive cell of the B lineage. It expresses leukosialin (CD43), CD 19, c-kit and surrogate receptor A encoded by VpreB and A5 genes associated with a glycoprotein complex gp35-gpl30. Pro-B cells differentiate into pre-B cells (pre-B II cells). The hallmark feature of this heterogeneous set of cells is the absence of surface immunoglobulin (Ig) and the presence of cytoplasmic /a chain. They also express major histocompatibility complex (MHC) class II antigens. Two discrete stages of differentiation have been distinguished in pre-B II cells: 1) cycling large pre-B cells which have lost c-kit expression and partially lost expression of CD43, express VA5 associated with /iH and express CD25; 2) resting small pre-B cells in which V[ (k and A) genes are rearranged and in which CD40 is expressed.

Pre-B cells differentiate into immature B cells expressing surface IgM, CD 19, CD25, CD40 and Fc and complement receptors. These cells differentiate into mature virgin B cells which lose CD25 but co-express IgM and IgD.

T cell lineage development is divided into three stages: the prethymic phase, the thymic phase, and the mature phase. The prethymic phase, during which multipotent stem cells develop into prethymic cells, begins with hematopoiesis in the fetal liver and then in bone marrow. These cells lack TCR as well as the CD4 and CD8 antigens, and are called double negative. Prethymic cells reach the thymus via the bloodstream, and enter by passing between endothelial cells in venules and then lodge in the medulla and at the corticomedullary junction. At the beginning of the thymic phase, cells divide rapidly and have the appearance of lymphoblasts and express a pre-T« receptor. Initially, these cells differentiate into lymphocytes which acquire both the CD4 and CDS antigens ('double-positive' cells) and then TCR and CD3. These cells give rise to CD4~ CD8 " and CD4 CD8+ mature lymphocytes.

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