Lymphocyte development Editorial overview Ellen Robey and Mark Schlissel 155 Current Opinion in Immunology 2003, 15:155–157 This review comes from a themed issue on Lymphocyte development Edited by Ellen Robey and Mark Schlissel 0952-7915/03/$ – see front matter ß 2003 Elsevier Science Ltd. All rights reserved. DOI 10.1016/S0952-7915(03)00017-7 Ellen Robey Division of Immunology, Department of Molecular and Cell Biology, 471 Life Science Addition, University of California at Berkeley, Berkeley, CA 94720-3200, USA e-mail: erobey@uclink4.berkeley.edu Ellen Robey’s laboratory is interested in cell-fate decisions in the immune system, with particular emphasis on thymic development. Mark Schlissel Division of Immunology, Department of Molecular and Cell Biology, 439 Life Science Addition, University of California at Berkeley, Berkeley, CA 94720-3200, USA e-mail: mss@uclink4.berkeley.edu Mark Schlissel’s laboratory studies the regulation of lymphocyte development and targeting of the V(D)J recombinase. Abbreviations AID activation-induced cytidine deaminase CSR class-switch recombination D diversity gene segment IL interleukin J joining gene segment NK natural killer SHM somatic hypermutation TCR T-cell receptor TNF tumor necrosis factor V variable gene segment During their development, lymphocytes acquire a remarkable ability to defend us from the universe of potential pathogens while maintaining tolerance to self. The study of lymphocyte development is important both for understanding how lymphocytes acquire their specificity and function, and for using as a model system of development. Indeed, the study of lymphocyte development involves the examination of diverse processes, including lineage commitment, gene regulation, receptor signaling, gene rearrangement, apoptosis and organogenesis. This section of Current Opinion in Immunology reviews a sample of the recent advances in each of these areas. Two articles in this section focus on one of the earliest events in lymphocyte development: the differentiation of hematopoietic stem cells into the committed progenitors that ultimately give rise to B cells, T cells and natural killer (NK) cells. Hardy [1] attempts to reconcile various studies that defined the earliest stages of development by using cell-surface markers. He goes on to consider the roles of various cytokines and their receptors, IL-7 in particular, in early differentiation events. Finally, Hardy considers exciting new work, which resulted in the definition of a hierarchy of transcriptional regulators that interact to promote developmental progression and lineage commitment. These transcriptional regulators include Pax-5, expression of which is necessary for B-lineage commitment, and Notch, which might play a corresponding role in T cells. The relationship between lineage choice and transcription factors is viewed in a novel and thought-provoking light by Warren and Rothenberg [2]. Avoiding the classical approach of focusing on the hypothesis that cell populations represent developmental intermediates, they concentrate instead on self-stabilizing regulatory networks of positive and negative transcription factors. In this model, the transition from an uncommitted to a committed state occurs by fluctuations in transcription factor levels, followed by a stabilization of intermediate states, and can occur by many www.current-opinion.com Current Opinion in Immunology 2003, 15:155–157