| First Author | Chan TD | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 5 | Pages | 893-904 |
| PubMed ID | 23142780 | Mgi Jnum | J:190871 |
| Mgi Id | MGI:5449813 | Doi | 10.1016/j.immuni.2012.07.017 |
| Citation | Chan TD, et al. (2012) Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen. Immunity 37(5):893-904 |
| abstractText | Secondary diversification of the B cell repertoire by immunoglobulin gene somatic hypermutation in the germinal center (GC) is essential for providing the high-affinity antibody specificities required for long-term humoral immunity. While the risk to self-tolerance posed by inadvertent generation of self-reactive GC B cells has long been recognized, it has not previously been possible to identify such cells and study their fate. In the current study, self-reactive B cells generated de novo in the GC failed to survive when their target self-antigen was either expressed ubiquitously or specifically in cells proximal to the GC microenvironment. By contrast, GC B cells that recognized rare or tissue-specific self-antigens were not eliminated, and could instead undergo positive selection by cross-reactive foreign antigen and produce plasma cells secreting high-affinity autoantibodies. These findings demonstrate the incomplete nature of GC self-tolerance and may explain the frequent association of cross-reactive, organ-specific autoantibodies with postinfectious autoimmune disease. |
