The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti–double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes.
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6 January 2003
Article|
January 06 2003
Secondary Heavy Chain Rearrangement : A Mechanism for Generating Anti–double-stranded DNA B Cells
Debora R. Sekiguchi,
Debora R. Sekiguchi
1Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104
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Robert A. Eisenberg,
Robert A. Eisenberg
1Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104
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Martin Weigert
Martin Weigert
2Department of Molecular Biology, Princeton University, Princeton, NJ 08544
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Debora R. Sekiguchi
1Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104
Robert A. Eisenberg
1Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104
Martin Weigert
2Department of Molecular Biology, Princeton University, Princeton, NJ 08544
Address correspondence to Dr. Martin Weigert, Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: 609-258-4698; Fax: 609-258-2205; E-mail: [email protected]
The online version of this article contains supplemental material.
*
Abbreviations used in this paper: B6, C57BL/6; cGVH, chronic graft-versus-host; ds, double-stranded; FWR, framework; KI, knock in; sd-tg, site-directed transgene; ss, single-stranded; tg, transgene.
Received:
May 07 2002
Revision Received:
October 15 2002
Accepted:
October 23 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (1): 27–39.
Article history
Received:
May 07 2002
Revision Received:
October 15 2002
Accepted:
October 23 2002
Citation
Debora R. Sekiguchi, Robert A. Eisenberg, Martin Weigert; Secondary Heavy Chain Rearrangement : A Mechanism for Generating Anti–double-stranded DNA B Cells . J Exp Med 6 January 2003; 197 (1): 27–39. doi: https://doi.org/10.1084/jem.20020737
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