Transcriptional control of early T and B cell developmental choices.
T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcription factor networks in which these E proteins are embedded are different both in membership and in architecture for T and B cell gene regulatory programs. These differences permit lineage commitment decisions to be made in different hierarchical orders. Furthermore, in contrast to B cell gene networks, the T cell gene network architecture for effector differentiation is sufficiently modular so that E protein inputs can be removed. Complete T cell-like effector differentiation can proceed without T cell receptor rearrangement or selection when E proteins are neutralized, yielding natural killer and other innate lymphoid cells.
Division of Biology, California Institute of Technology, Pasadena, California 91125; email: evroth@its.caltech.edu.
Ellen V
EV
Rothenberg
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch