Despite the tremendous diversity of the cells of the hematopoietic system, 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.
Table of ContentsPart I: Stem Cells and Lineage Commitment Models. Developmental Origins of Hematopoietic Stem Cells,Elaine Dzierzak and Alexander Medvinsky . Self-Renewal of Stem Cells: The Intrinsic Timetable Model, Peter Lansdorp. Transcription Factors Regulating Early Hematopoietic Development and Lineage Commitment,Stuart H. Orkin. Part II: Intrinsic Factors Regulating B and T Lymphopoiesis.The Ikaros Gene Family in Hemopoietic Differentiation, Nicole Avitahl, Aliki Nichogiannopoulou, Katia Georgopoulos, and Susan Winandy. Transcriptional Control of B-Cell Differentiation by EBF and E2A, Mikael Sigvardsson and Rudolf Grosschedl. Role of the Transcription Factor BSAP (Pax-5) in B-Cell Development, Meinrad Busslinger and Stephen L. Nutt.The Role of PU.1 in the Regulation of Lymphoid and Myeloid Hematopoietic Progenitors, Edward W. Scott Chromatin Structure and Lineage Determination, Dimitris Kioussis and Richard Festenstein . Part III: Extrinsic Factors Regulating B and T Lymphoiesis. The Role of Cytokines in Hematolymphoid Development, Tannishtha Reya and Simon R. Carding .Life/Death Decisions in B-Lymphocyte Precursors: A Role for Cytokines, Cell Interaction Molecules, and Hormones, Paul W. Kincade, Kay Medina, Glennda Smithson, Zhong Zheng, Kenji Oritani, Lisa Borghesi, Yoshio Yamashita, Kimberly Payne, and Takaichi Shimozato . Regulation of Lymphocyte Development by Microenvironmental and Systemic Factors,Encarnacion Montecino-Rodriguez and Kenneth Dorshkind . Cytokines and Chemokines in T-Cell Development,Albert Zlotnik, Myriam Capone, and Alain P. Vicari . Cytokine and Stromal Influences on Early B-Cell Development,Lisa J. Jarvis and Tucker W. LeBien . Part IV: Commitment and Ordered Progression in Development of Lymphoid Lineages. Staging B-Cell Development and the Role of Ig Gene Arrangement in B-Lineage Progression,Richard R. Hardy, Susan Shinton, Robert Wasserman, and Yue-Sheng Li . Lineage Relationships Between B Lymphocytes and Macrophages,Barbara L. Kee and Christopher J. Paige .TCR-Independent Development of Pluripotent T-Cell Precursors, Li Wu, Ferenc Livak, and Howard T. Petrie . T-Cell Development from Hematopoietic Stem Cells, Koichi Akashi, Motonari Kondo, Annette M. Schlageter, and Irving L. Weissman . Gene Regulation in T-Cell Lineage Committment, Ellen V. Rothenberg . The ab/gð Lineage Decision: An Evaluation of the 'T-Cell Receptor Determinant,' 'Progenitor Precommitment,' or 'Codeterminant ' Models, Eric S. Hoffman, Lorena Passoni, Erastus C. Dudley, Michael Girardi, and Adrian Hayday . Part V: Selection Processes Operating During B-Lymphocyte Development. Structure and Function of the Pro- and Pre-B-Cell Receptors on B-Lymphoid Lineage Precursor Cells, Thomas H. Winkler and Fritz Melchers . Molecular Mechanisms Regulating Negative Selection in Immature-Stage B-Cells,Leslie B. King, Peter Sandel, Richard A. Sater, and John G. Monroe . Part VI: Selection Processes Operating DuringT-Lymphocyte Development. How Essential Is the Pre-T-Cell Receptor? Jan Buer and Harald von Boehmer. Developmental Stage-Specific Responses to Ligation of CD3-Containing Complexes, Christiaan N. Levelt . The Molecular Basis of Thymocyte Positive Selection and CD4/CD8 Lineage Commitment, Cynthia J. Guidos . Part VII: Clinical Applications of Hematolymphoid Development. Stem Cell Transplants for Hematopoietic Malignancies, Susan C. Guba and Bart Barlogie . Placental Blood: Immunology, Transplantation, and Gene Therapy, Anne F. Eder and Leslie E. Silberstein. Human Hematopoietic Stem Cells, Progenitors, and Peripheral Blood Lymphocytes as Targets for the Correction of Immune System Disorders via Gene Therapy,Karen E. Pollok and David A.Williams. Index.