University of Massachusetts Medical School, Department of Molecular Genetics and Microbiology
Animals; B-Lymphocytes; Base Sequence; DNA Primers; Flow Cytometry; Hematopoietic Stem Cells; Immunoglobulin Heavy Chains; Mice; Mice, Inbred C57BL; Mice, Knockout; Polymerase Chain Reaction; Recombination, Genetic; VDJ Recombinases
Microbiology | Molecular Genetics
In B lineage progenitors, V(D)J recombination occurs only during distinct stages of development and is restricted to immunoglobulin loci. This process is thought to be controlled by both regulated expression of the V(D)J recombinase and by limited accessibility of target loci to the recombinase complex. However, it is unknown whether these two processes occur concomitantly in developing B lineage progenitors or whether these events are temporally distinct and, therefore, potentially independently regulated. To distinguish between these possibilities, we developed a transgenic V(D)J recombination substrate that is not governed by the same chromatin remodeling constraints as endogenous immunoglobulin heavy chain (IgH) loci and examined the requirements for V(D)J recombination to initiate in early B lineage progenitors. We find that single B lineage precursors express an active V(D)J recombinase in vivo before the stage when IgH rearrangements are frequently detectable. Our results indicate that the onset of recombinase activity and the initiation of IgH recombination are developmentally distinct events in the B lineage.
DOI of Published Version
J Exp Med. 2004 Feb 16;199(4):483-9. Epub 2004 Feb 9. Link to article on publisher's site
The Journal of experimental medicine
Borghesi, Lisa A. and Gerstein, Rachel M., "Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo" (2004). Open Access Articles. 1034.