We are upgrading the repository! A content freeze is in effect until December 6, 2024. New submissions or changes to existing items will not be allowed during this period. All content already published will remain publicly available for searching and downloading. Updates will be posted in the Website Upgrade 2024 FAQ in the sidebar Help menu. Reach out to escholarship@umassmed.edu with any questions.
B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors
Authors
Borghesi, Lisa A.Hsu, Lih-Yun
Miller, Juli P.
Anderson, Michael
Herzenberg, Leonard A.
Herzenberg, Leonore A.
Schlissel, Mark S.
Allman, David M.
Gerstein, Rachel M.
UMass Chan Affiliations
Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2004-02-11Keywords
AnimalsB-Lymphocytes
Green Fluorescent Proteins
Hematopoietic Stem Cells
Homeodomain Proteins
Luminescent Proteins
Lymphopoiesis
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Polymerase Chain Reaction
VDJ Recombinases
Microbiology
Molecular Genetics
Metadata
Show full item recordAbstract
Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate the recombinase in multipotent hematopoietic progenitors. Using mice that express a fluorescent transgenic V(D)J recombination reporter, we show that the V(D)J recombinase is active as early as common lymphoid progenitors (CLPs) but not in the upstream progenitors that retain myeloid lineage potential. Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP. By single cell PCR, we demonstrate that V(D)J rearrangements are detectable at IgH loci in approximately 5% of splenic natural killer cells. Finally, we show that recombinase activity in CLPs is largely controlled by the Erag enhancer. As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors.Source
J Exp Med. 2004 Feb 16;199(4):491-502. Epub 2004 Feb 9. Link to article on publisher's siteDOI
10.1084/jem.20031800Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38152PubMed ID
14769852Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1084/jem.20031800