The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online December 3, 2007
doi:10.1084/jem.20071224
The Journal of Experimental Medicine, Vol. 204, No. 13, 3195-3208
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Davila et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3285K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Davila, M.
Right arrow Articles by Kelsoe, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davila, M.
Right arrow Articles by Kelsoe, G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro–B cells

Marco Davila1, Feifei Liu1, Lindsay G. Cowell2, Anne E. Lieberman2, Emily Heikamp1, Anjali Patel1, and Garnett Kelsoe1

Departments of Immunology1 and Biostatistics and Bioinformatics2 , Duke University, Durham, NC 27710

CORRESPONDENCE Garnett Kelsoe: ghkelsoe{at}duke.edu

Receptor editing is believed to play the major role in purging newly formed B cell compartments of autoreactivity by the induction of secondary V(D)J rearrangements. In the process of immunoglobulin heavy (H) chain editing, these secondary rearrangements are mediated by direct VH-to-JH joining or cryptic recombination signals (cRSs) within VH gene segments. Using a statistical model of RS, we have identified potential cRSs within VH gene segments at conserved sites flanking complementarity-determining regions 1 and 2. These cRSs are active in extrachromosomal recombination assays and cleaved during normal B cell development. Cleavage of multiple VH cRSs was observed in the bone marrow of C57BL/6 and RAG2:GFP and µMT congenic animals, and we determined that cRS cleavage efficiencies are 30–50-fold lower than a physiological RS. cRS signal ends are abundant in pro–B cells, including those recovered from µMT mice, but undetectable in pre– or immature B cells. Thus, VH cRS cleavage regularly occurs before the generation of functional preBCR and BCR. Conservation of cRSs distal from the 3' end of VH gene segments suggests a function for these cryptic signals other than VH gene replacement.

Abbreviations used: BCR, B cell antigen receptor; CDR, complementarity determining region; cRS, cryptic recombination signal; Cys, cysteine; FW, Ig frame work region; LM, ligation-mediated; RIC, RS information content; RS, physiological recombination signal; SDT, site-directed transgene; SE, signal end.

M. Davila and F. Liu contributed equally to this paper.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS