title: Signaling circuits in early B-cell development.
abstract: Early B-cell development is an ordered and highly regulated process with alternating phases of cell proliferation and differentiation leading to B cells with the ability to recognize an extraordinarily large repertoire of different antigens. Here, we discuss what is currently known about the receptors in B-cell progenitors and how their signaling pathways influence immunoglobulin (Ig) gene rearrangement and the transcriptional program of early B cells. In particular, we address the interplay of the interleukin-7 receptor and the pre-B-cell receptor (preBCR) in shaping the survival, proliferation, and differentiation of early B cells. Each receptor addresses a unique set of signaling components but they also share signaling pathways, most prominently the MAPK/Erk and phosphoinositide-3 kinase pathways. The latter pathway regulates transcription factors of the FoxO family that play a central role in the proliferation to differentiation switch of pre-B cells. Interestingly, these two alternative cellular programs (proliferation and differentiation) are both controlled by the preBCR. Finally, we discuss how mutations or alterations of these pathways result in deregulated pre-B-cell expansion and leukemia.
authors: BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany; Department of Molecular Immunology, BioIII, Faculty of Biology, Albert-Ludwigs-Universität Freiburg and Max Planck Institute for Immunobiology and Epigenetic Stübeweg 51, Freiburg, Germany. Electronic address: michael.reth@bioss.uni-freiburg.de.
authors: Michael
authors: M
authors: Reth
authors: BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany; Department of Molecular Immunology, BioIII, Faculty of Biology, Albert-Ludwigs-Universität Freiburg and Max Planck Institute for Immunobiology and Epigenetic Stübeweg 51, Freiburg, Germany.
authors: Peter
authors: P
authors: Nielsen
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D054420:Pre-B Cell Receptors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D054420:Pre-B Cell Receptors
keywords: B-cell development; Il7 receptor; MAP kinase; PI3 kinase; Signaling; preB receptor