Somatic mutation and light chain rearrangement generate autoimmunity in anti-single-stranded DNA transgenic MRL/lpr mice

Citation
F. Brard et al., Somatic mutation and light chain rearrangement generate autoimmunity in anti-single-stranded DNA transgenic MRL/lpr mice, J EXP MED, 190(5), 1999, pp. 691-704
Citations number
48
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
00221007 → ACNP
Volume
190
Issue
5
Year of publication
1999
Pages
691 - 704
Database
ISI
SICI code
0022-1007(19990906)190:5<691:SMALCR>2.0.ZU;2-H
Abstract
Antibodies to single-stranded (ss)DNA are expressed in patients with system ic lupus erythematosus and in lupus-prone mouse models such as the MRL/Mp-l pr/lpr (MRL/lpr) strain. In nonautoimmune mice, B cells bearing immunoglobu lin site-directed transgenes (sd-tgs) that code for anti-ssDNA are function ally silenced. In MRL/lpr autoimmune mice, the same sd-tgs are expressed in peripheral B cells and these autoantibodies gain the ability to bind other autoantigens such as double-stranded DNA and cell nuclei. These new specif icities arise by somatic mutation of the anti-ssDNA sd-tgs and by secondary light chain rearrangement. Thus, B cells that in normal mice are anergic c an be activated in MRL/lpr mice, which can lead to the generation of pathol ogic autoantibodies. In this paper, we provide the first direct evidence fo r peripheral rearrangement in vivo.