| First Author | Umiker BR | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 10 | Pages | 3093-108 |
| PubMed ID | 25044405 | Mgi Jnum | J:336602 |
| Mgi Id | MGI:6855567 | Doi | 10.1002/eji.201344282 |
| Citation | Umiker BR, et al. (2014) Production of IgG autoantibody requires expression of activation-induced deaminase in early-developing B cells in a mouse model of SLE. Eur J Immunol 44(10):3093-108 |
| abstractText | Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG antinuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG antinucleic acid Abs. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicda(tg) ), either in all B cells or only in mature B cells. Here, we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early-developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early-developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation, contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early-developing B cells. |
