| First Author | Simoni L | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 5 | Pages | 108330 |
| PubMed ID | 33147456 | Mgi Jnum | J:301308 |
| Mgi Id | MGI:6489160 | Doi | 10.1016/j.celrep.2020.108330 |
| Citation | Simoni L, et al. (2020) Complement C4A Regulates Autoreactive B Cells in Murine Lupus. Cell Rep 33(5):108330 |
| abstractText | Systemic lupus erythematosus (SLE) is a severe autoimmune disease mediated by pathogenic autoantibodies. While complement protein C4 is associated with SLE, its isoforms (C4A and C4B) are not equal in their impact. Despite being 99% homologous, genetic studies identified C4A as more protective than C4B. By generating gene-edited mouse strains expressing either human C4A or C4B and crossing these with the 564lgi lupus strain, we show that, overall, C4A-like 564Igi mice develop less humoral autoimmunity than C4B-like 564Igi mice. This includes a decrease in the number of GCs, autoreactive B cells, autoantibodies, and memory B cells. The higher efficiency of C4A in inducing self-antigen clearance is associated with the follicular exclusion of autoreactive B cells. These results explain how the C4A isoform is protective in lupus and suggest C4A as a possible replacement therapy in lupus. |
