Despite the tremendous diversity of the cells of the hematopoietic system
Despite the tremendous diversity of the cells of the hematopoietic system Lipo 2000 Transfection Reagent, they are all derived from common precursor cells that are generated in the fetus and persist into adult life. In this regard, Band T lymphocytes, which comprise the two arms of the antigen-specific and inducible immune system, though functionally very different, are descendants of the same stem cell precursor. In the past several years, we have witnessed an explosion of information regarding the process by which differentiation of B- and T-cells from stem cells occurs. This information, like the answers to most important biological questions, has come from multiple and diverse directions. Because all hematopoietic cells arise from common precursors, complex regulatory processes must be involved in determining commitment to various lineages. Understanding commitment to the B- or T-cell lineage remains incomplete; however, identification of transcription factors necessary for progression along specific B- and T-cell pathways suggests that we are on the verge of understanding the molecules involved in the initial fate-determining steps. Studies of this type previously could be accomplished only in nonmammalian systems that are more amenable to genetic approaches. However, new technologies allow increasingly elegant and informative studies in mammalian systems, particularly for cells of the hematopoietic system.
At the level of cell biology, significant progress has been made in the identification and characterization of hematopoietic stem cells and developmental stages associated with B- and T-cell development. Two advances have contributed to this progress. One is the ability to use constellations of cell-surface markers to provide extraordinary precision in the developmental characterization of individual cells. The other is the ability to culture and transfer hematopoietic cells in a variety of environments, and to define the responses of individual cells by cell-autonomous markers. As a result of these advances, cell transfer experiments with tightly defined precursor populations have even begun to dissect the process of commitment to B- and T-cell lineages, providing new evidence for a gradual, stepwise narrowing of developmental potential. T- and natural killer cells appear to be more closely related, by this measure, than Tand B-cells; whereas T- and most myeloerythroid cells appear much less closely related. These relationships provide a starting point for defining the target genes on which lineage-determining factors must work in driving commitment. B- and T-cells are distinct from other hematopoietic cells in that the fully developed progeny are clonally unique. In order to avoid retention of nonfunctional or autoreactive clones, antigen receptor-mediated inducible selection events occur during defined stages in the development of these cells. These events, both positive and negative, are central to establishing the available immune system repertoire. Genetic, biochemical, and cellular approaches are each producing important insights into the molecular basis and cellular mechanisms underlying these selection events. In the past, B- and T-cell malignancies have provided our only chance to study early stages of development of these cells. Cells “frozen” at particular stages of development by malignant transformation provided tools to study the phenotype and cell biology of developing B- and T-cells. Now, however, the ability to isolate normal cells at defined developmental stages affords us the ability to define the cell biology of these cells and thereby better understand the physiology of their transformed cell counterparts.
The usefulness of this information lies in our ability to use it to alter the growth characteristics of specific B- and T-cell malignancies. Finally, cells of the developing hematopoietic system are especially amenable to gene therapy approaches. Because they are now easily isolatable, capable of expansion, and relatively easy to maintain in culture, they provide convenient vehicles for the introduction of new genes. Significant progress has been realized in all of the above areas over the past several years. This progress has yielded not only important insights into significant and fundamental areas of cell biology cck8, but has influenced our thinking in terms of understanding human disease and new ways of therapeutic intervention into disease processes cck8 formula. The aim of Molecular Biology of B-Cell and T-Cell Development is to present an integrated and comprehensive presentation of these new advances in Band T lymphocyte development. Topics covered in this volume will be of interest to researchers and clinicians interested in hematopoiesis, immunology, cancer biology, and gene therapy.
