| First Author | Degn SE | Year | 2017 |
| Journal | Cell | Volume | 170 |
| Issue | 5 | Pages | 913-926.e19 |
| PubMed ID | 28841417 | Mgi Jnum | J:247831 |
| Mgi Id | MGI:5926954 | Doi | 10.1016/j.cell.2017.07.026 |
| Citation | Degn SE, et al. (2017) Clonal Evolution of Autoreactive Germinal Centers. Cell 170(5):913-926.e19 |
| abstractText | Germinal centers (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the production of high-affinity antibodies. This response is a central driver of pathogenesis in autoimmune diseases, such as systemic lupus erythematosus (SLE), but the natural history of autoreactive GCs remains unclear. Here, we present a novel mouse model where the presence of a single autoreactive B cell clone drives the TLR7-dependent activation, expansion, and differentiation of other autoreactive B cells in spontaneous GCs. Once tolerance was broken for one self-antigen, autoreactive GCs generated B cells targeting other self-antigens. GCs became independent of the initial clone and evolved toward dominance of individual clonal lineages, indicating affinity maturation. This process produced serum autoantibodies to a breadth of self-antigens, leading to antibody deposition in the kidneys. Our data provide insight into the maturation of the self-reactive B cell response, contextualizing the epitope spreading observed in autoimmune disease. |
