The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 151K)
Right arrow PPT slides of all figures
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 Retter, M. W.
Right arrow Articles by Nemazee, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Retter, M. W.
Right arrow Articles by Nemazee, D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/10/1231/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 7, October 5, 1998 1231-1238

Articles

Receptor Editing Occurs Frequently during Normal B Cell Development

Marc W. Retter* and David Nemazee*,{ddagger}

From the * National Jewish Medical and Research Center, Division of Basic Sciences, Department of Pediatrics, Denver, Colorado 80206; and the {ddagger} University of Colorado Health Science Center, Department of Immunology, Denver, Colorado 80220

Allelic exclusion is established in development through a feedback mechanism in which the assembled immunoglobulin (Ig) suppresses further V(D)J rearrangement. But Ig expression sometimes fails to prevent further rearrangement. In autoantibody transgenic mice, reactivity of immature B cells with autoantigen can induce receptor editing, in which allelic exclusion is transiently prevented or reversed through nested light chain gene rearrangement, often resulting in altered B cell receptor specificity. To determine the extent of receptor editing in a normal, non-Ig transgenic immune system, we took advantage of the fact that {lambda} light chain genes usually rearrange after {kappa} genes. This allowed us to analyze {kappa} loci in IgM{lambda}+ cells to determine how frequently in-frame {kappa} genes fail to suppress {lambda} gene rearrangements. To do this, we analyzed recombined V{kappa}J{kappa} genes inactivated by subsequent recombining sequence (RS) rearrangement. RS rearrangements delete portions of the {kappa} locus by a V(D)J recombinase-dependent mechanism, suggesting that they play a role in receptor editing. We show that RS recombination is frequently induced by, and inactivates, functionally rearranged {kappa} loci, as nearly half (47%) of the RS-inactivated V{kappa}J{kappa} joins were in-frame. These findings suggest that receptor editing occurs at a surprisingly high frequency in normal B cells.

Key Words: receptor editing • recombining sequence recombination • immune tolerance • B lymphocytes • V(D)J rearrangements

Address correspondence to David Nemazee, The Scripps Research Institute, Mail drop IMM-29, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 619-784-9528; Fax: 619-784-8805; E-mail: nemazee{at}scripps.edu

Abbreviations used: FWR, framework region; JC{kappa}D/+, heterozygous {kappa} deficient germline genotype; RS, recombining sequence; Tg, transgenic.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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