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, 639K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brard, F.
Right arrow Articles by Weigert, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brard, F.
Right arrow Articles by Weigert, M.
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, 0022-1007/1999/9/691/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 5, September 6, 1999 691-704

Original Article

Somatic Mutation and Light Chain Rearrangement Generate Autoimmunity in Anti–Single-Stranded DNA Transgenic Mrl/lpr Mice

Frederic Brarda, Michele Shannona, Eline Luning Prakb, Samuel Litwinc, and Martin Weigerta

a From the Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544
b Department of Pathology and Laboratory Medicine and the Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
c Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544.609-258-2205609-258-2683

mweigert{at}molbio.princeton.edu

Antibodies to single-stranded (ss)DNA are expressed in patients with systemic lupus erythematosus and in lupus-prone mouse models such as the MRL/Mp-lpr/lpr (MRL/lpr) strain. In nonautoimmune mice, B cells bearing immunoglobulin site-directed transgenes (sd-tgs) that code for anti-ssDNA are functionally silenced. In MRL/lpr autoimmune mice, the same sd-tgs are expressed in peripheral B cells and these autoantibodies gain the ability to bind other autoantigens such as double-stranded DNA and cell nuclei. These new specificities arise by somatic mutation of the anti-ssDNA sd-tgs and by secondary light chain rearrangement. Thus, B cells that in normal mice are anergic can be activated in MRL/lpr mice, which can lead to the generation of pathologic autoantibodies. In this paper, we provide the first direct evidence for peripheral rearrangement in vivo.

Key Words: anti-DNA • B cell tolerance • receptor editing • systemic lupus erythematosus • VH replacement

1used in this paper: ANA, antinuclear antibody; dsDNA, double-stranded DNA; FW, framework; HEL, hen egg lysozyme; MRL/lpr, MRL/Mp-lpr/lpr mouse; RAG, recombination-activating gene; sd-tg, site-directed transgene; ssDNA, single-stranded DNA

© 1999 The Rockefeller University Press


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?




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