Please use this identifier to cite or link to this item: 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
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