The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Radic, M. Z.
Right arrow Articles by Weigert, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Radic, M. Z.
Right arrow Articles by Weigert, M.

The Journal of Immunology, Vol 155, Issue 6 3213-3222, Copyright © 1995 by American Association of Immunologists

ARTICLES

Constitutive secretion of transgene-encoded IgG2b autoantibodies leads to symptoms of autoimmune disease

MZ Radic, SM Ibrahim, J Rauch, SA Camper and M Weigert
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129, USA.

Anti-DNA Ab are strictly regulated, except in autoimmunity, where they are expressed and may contribute to pathogenicity. To study constitutive anti-DNA Ab secretion in nonautoimmune mice, two anti- dsDNA H/L chain transgene combinations were constructed using an IgG2b C region with secretory but no transmembrane domain exons. One H/L combination, consisting of the VH3H9 H and V kappa 4 L chain transgenes, was chosen to recreate 3H9, an autoantibody that originally arose in an autoimmune MRL/lpr mouse; the other paired a higher affinity variant of VH3H9, 56R, with the same V kappa 4 L chain. Elevated titers of IgG2b along with normal levels of other isotypes were observed in transgene-positive mice, indicating that constitutive transgene-directed Ab secretion was achieved. Sera and hybridoma supernatants from VH3H9 gamma transgene-positive animals exhibited binding to dsDNA, ssDNA, and cardiolipin. Mice expressing the 56R gamma H chain and the V kappa 4 L chain showed enhanced binding. Expression of the transgenes correlated with signs of autoimmune disease, including prolonged plasma clotting in vitro, and reduced litter size. The results suggest that even a single autoreactive H chain that escapes tolerance may suffice to induce features of autoimmune disease.


This article has been cited by other articles:


Home page
 J. Immunol.Home page
W.-H. Shao, R. A. Eisenberg, and P. L. Cohen
The Mer Receptor Tyrosine Kinase Is Required for the Loss of B Cell Tolerance in the Chronic Graft-versus-Host Disease Model of Systemic Lupus Erythematosus
J. Immunol., June 1, 2008; 180(11): 7728 - 7735.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
D. Yuan, R. Bibi, and T. Dang
The role of adjuvant on the regulatory effects of NK cells on B cell responses as revealed by a new model of NK cell deficiency
Int. Immunol., May 1, 2004; 16(5): 707 - 716.
[Abstract] [Full Text] [PDF]

Home page
 LupusHome page
C T Ravirajan and D A Isenberg
Transgenic models of tolerance and autoimmunity: with special reference to systemic lupus erythematosus
Lupus, December 1, 2002; 11(12): 843 - 849.
[Abstract] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Boes, T. Schmidt, K. Linkemann, B. C. Beaudette, A. Marshak-Rothstein, and J. Chen
Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM
PNAS, February 1, 2000; 97(3): 1184 - 1189.
[Abstract] [Full Text] [PDF]

Home page
 LupusHome page
F.K. Stevenson and G.J. Silverman
Expression of anti-DNA antibodies
Lupus, January 1, 1997; 6(3): 321 - 323.
[PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.