title: Cutting edge: cell-autonomous control of IL-7 response revealed in a novel stage of precursor B cells.
abstract: During early stages of B-lineage differentiation in bone marrow, signals emanating from IL-7R and pre-BCR are thought to synergistically induce proliferative expansion of progenitor cells. Paradoxically, loss of pre-BCR-signaling components is associated with leukemia in both mice and humans. Exactly how progenitor B cells perform the task of balancing proliferative burst dependent on IL-7 with the termination of IL-7 signals and the initiation of L chain gene rearrangement remains to be elucidated. In this article, we provide genetic and functional evidence that the cessation of the IL-7 response of pre-B cells is controlled via a cell-autonomous mechanism that operates at a discrete developmental transition inside Fraction C' (large pre-BII) marked by transient expression of c-Myc. Our data indicate that pre-BCR cooperates with IL-7R in expanding the pre-B cell pool, but it is also critical to control the differentiation program shutting off the c-Myc gene in large pre-B cells.
authors: Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Gabriel J
authors: GJ
authors: Sandoval
authors: Daniel B
authors: DB
authors: Graham
authors: Deepta
authors: D
authors: Bhattacharya
authors: Barry P
authors: BP
authors: Sleckman
authors: Ramnik J
authors: RJ
authors: Xavier
authors: Wojciech
authors: W
authors: Swat
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D055879:Gene Knock-In Techniques; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D006131:Growth Inhibitors; D015851:Interleukin-7; D016271:Proto-Oncogene Proteins c-myc; D020395:Receptors, Interleukin-7