An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system.
Abstract
Understanding immune tolerance mechanisms is a major goal of immunology research,
but mechanistic studies have generally required the use of mouse models carrying untargeted
or targeted antigen receptor transgenes, which distort lymphocyte development and
therefore preclude analysis of a truly normal immune system. Here we demonstrate an
advance in in vivo analysis of immune tolerance that overcomes these shortcomings.
We show that custom superantigens generated by single chain antibody technology permit
the study of tolerance in a normal, polyclonal immune system. In the present study
we generated a membrane-tethered anti-Igkappa-reactive single chain antibody chimeric
gene and expressed it as a transgene in mice. B cell tolerance was directly characterized
in the transgenic mice and in radiation bone marrow chimeras in which ligand-bearing
mice served as recipients of nontransgenic cells. We find that the ubiquitously expressed,
Igkappa-reactive ligand induces efficient B cell tolerance primarily or exclusively
by receptor editing. We also demonstrate the unique advantages of our model in the
genetic and cellular analysis of immune tolerance.
Type
Journal articleSubject
AnimalsAutoantigens
B-Lymphocytes
Bone Marrow Cells
Bone Marrow Transplantation
Cell Line, Tumor
Genes, RAG-1
Immune System
Immune Tolerance
Immunoglobulin kappa-Chains
Immunoglobulin lambda-Chains
Mice
Mice, Knockout
Mice, Transgenic
Mutation
Proto-Oncogene Proteins c-bcl-2
Rats
Recombinant Fusion Proteins
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https://hdl.handle.net/10161/8353Published Version (Please cite this version)
10.1084/jem.20041854Publication Info
Ait-Azzouzene, Djemel; Verkoczy, Laurent; Peters, Jorieke; Gavin, Amanda; Skog, Patrick;
Vela, José Luis; & Nemazee, David (2005). An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance
through receptor editing in a normal polyclonal immune system. J Exp Med, 201(5). pp. 817-828. 10.1084/jem.20041854. Retrieved from https://hdl.handle.net/10161/8353.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Laurent Karl Verkoczy
Adjunct Professor in the Department of Medicine
Laurent Verkoczy, PhD is Associate Professor of Medicine and Pathology at Duke University
Medical Center. Dr.Verkoczy directs the Laboratory of B-cell Immunoregulation at the
Duke Human Vaccine Institute and also serves as a B-cell Focus Investigator in Duke’s
Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID) consortium.
He obtained his Ph.D. in Immunology from the University of Toronto in 2000 and completed
post-doctoral studies at The S
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.

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