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
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.