| First Author | Brard F | Year | 1999 |
| Journal | J Exp Med | Volume | 190 |
| Issue | 5 | Pages | 691-704 |
| PubMed ID | 10477553 | Mgi Jnum | J:57612 |
| Mgi Id | MGI:1345006 | Doi | 10.1084/jem.190.5.691 |
| Citation | Brard F, et al. (1999) Somatic mutation and light chain rearrangement generate autoimmunity in anti-single-stranded DNA transgenic MRL/lpr mice. J Exp Med 190(5):691-704 |
| abstractText | Antibodies to single-stranded (ss)DNA are expressed in patients with systemic lupus erythematosus and in lupus-prone mouse models such as the MRL/Mp-lpr/lpr (MRL/lpr) strain. In nonautoimmune mice, B cells bearing immunoglobulin site-directed transgenes (sd-tgs) that code for anti-ssDNA are functionally 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 specificities 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 can be activated in MRL/lpr mice, which can lead to the generation of pathologic autoantibodies. In this paper, we provide the first direct evidence for peripheral rearrangement in vivo. |
