期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 1, 页码 27-39出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20020737
关键词
SLE; autoimmunity; anti-dsDNA; B lymphocytes; graft vs. host
资金
- NIAID NIH HHS [U19-AI446358/03] Funding Source: Medline
- NIAMS NIH HHS [T32 AR007442, AR26574, R01 AR034156, AR34156, T32 AR07442] Funding Source: Medline
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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