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Productive Coupling of Accessible V 14 Segments and DJ Complexes Determines the Frequency
 

Summary: Productive Coupling of Accessible V 14 Segments
and DJ Complexes Determines the Frequency
of V 14 Rearrangement1
Sheila Ranganath,* Andrea C. Carpenter,
Megan Gleason,* Albert C. Shaw,2
*
Craig H. Bassing,3
and Frederick W. Alt3
*
To elucidate mechanisms that regulate V rearrangement, we generated and analyzed mice with a V(D)J recombination reporter
cassette of germline D -J segments inserted into the endogenous V 14 locus (V 14Rep
). As a control, we first generated and
analyzed mice with the same D -J cassette targeted into the generally expressed c-myc locus (c-mycRep
). Substantial c-mycRep
recombination occurred in both T and B cells and initiated concurrently with endogenous D to J rearrangements in thymocytes.
In contrast, V 14Rep
recombination was restricted to T cells and initiated after endogenous D to J rearrangements, but
concurrently with endogenous V 14 rearrangements. Thus, the local chromatin environment imparts lineage and developmental
stage-specific accessibility upon the inserted reporter. Although V 14 rearrangements occur on only 5% of endogenous TCR
alleles, the V 14Rep

  

Source: Alt,, Frederick - Immune Disease Institute, Harvard University

 

Collections: Biology and Medicine