|
|
|
|
|
|
|
||
Original Article |
1 Locus in Scid Mice
MJ_Bosma{at}fccc.edu
In severe combined immunodeficient (scid) mice, V(D)J recombination is severely impaired due to a recessive mutation (scid). Thus, we were surprised to find in this study that V
1–J1 rearrangement is routinely detectable in scid fetal liver, adult bone marrow, and spleen in the apparent absence of completed VH–DJH and V
–J rearrangements. Particularly surprising, we found the level of V1–J1 rearrangement in scid fetal liver to be comparable to that in fetal liver of wild-type mice. The majority of scid V1–J1 rearrangements contained abnormal deletions at the VJ junction, consistent with the known effect of scid. However, 
15% of V1–J1 rearrangements lacked abnormal deletions. Productive 1 transcripts resulting from in-frame rearrangements were readily detectable in scid adult bone marrow and spleen, consistent with our ability to detect 1-expressing cells by flow cytometry in the spleens of bcl-2–transgenic scid mice. Strikingly, 1 transcripts from individual scid mice often showed VJ junctional sequences with the same recurring palindromic (P) additions of three, four, or five nucleotides. To account for these findings, we suggest that (a) nonhomologous end joining of V1 and J1 coding ends in fetal B lineage cells may not be (severely) impaired by scid; (b) recurring P additions in scid 1 transcripts may reflect certain molecular constraints imposed by scid on the resolution of V1 and J1 hairpin coding ends; and (c), scid lymphocytes with productively rearranged V1 and J1 elements may differentiate into recombinase-inactive cells and emigrate from bone marrow to spleen.
Key Words: B cell differentiation • pro-B cells • premature Ig recombination • VJ junctional diversity • P additions
© 2000 The Rockefeller University Press
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| TABLE OF CONTENTS |
|
