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Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells.

ABSTRACT: 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.

SUBMITTER: Sekiguchi DR

PROVIDER: S-EPMC2193805 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells.

Sekiguchi Debora R DR Eisenberg Robert A RA Weigert Martin M

The Journal of experimental medicine 20030101 1

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) D ...[more]

PMID: 12515811

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