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https://doi.org/10.1371/journal.pbio.0030082
Title: | Basal immunoglobulin signaling actively maintains developmental stage in immature B cells | Authors: | Tze L.E. Schram B.R. Lam K.-P. Hogquist K.A. Hippen K.L. Liu J. Shinton S.A. Otipoby K.L. Rodine P.R. Vegoe A.L. Kraus M. Hardy R.R. Schlissel M.S. Rajewsky K. Behrens T.W. |
Keywords: | androstane derivative cre recombinase green fluorescent protein herbimycin A immunoglobulin immunoglobulin heavy chain immunoglobulin light chain immunoglobulin M immunoglobulin M pharmacology phosphatidylinositol 3 kinase inhibitor protein tyrosine kinase inhibitor wortmannin wortmannin allele animal animal cell article B lymphocyte B lymphocyte bone marrow cell cell culture cell maturation conference paper controlled study cytology developmental stage drug effect gene rearrangement gene rearrangement genetics immunology incubation time mouse mouse mouse mutant nonhuman nucleotide sequence physiology plasticity signal transduction signal transduction transgenic mouse Androstadienes Animals B-Lymphocytes Bone Marrow Cells Cells, Cultured cytology drug effects Gene Rearrangement Gene Rearrangement, B-Lymphocyte genetics genetics genetics Green Fluorescent Proteins Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulin M Immunoglobulins immunology immunology immunology immunology Mice Mice, Knockout Mice, Transgenic pharmacology physiology Signal Transduction |
Issue Date: | 2005 | Publisher: | Public Library of Science | Citation: | Tze L.E., Schram B.R., Lam K.-P., Hogquist K.A., Hippen K.L., Liu J., Shinton S.A., Otipoby K.L., Rodine P.R., Vegoe A.L., Kraus M., Hardy R.R., Schlissel M.S., Rajewsky K., Behrens T.W. (2005). Basal immunoglobulin signaling actively maintains developmental stage in immature B cells. PLoS Biology 3 (3) : 463-475. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.0030082 | Abstract: | In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking "back-differentiation" of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. © 2005 Tze et al. | Source Title: | PLoS Biology | URI: | https://scholarbank.nus.edu.sg/handle/10635/165427 | ISSN: | 15449173 | DOI: | 10.1371/journal.pbio.0030082 |
Appears in Collections: | Staff Publications Elements |
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