Autoreactive Germinal Centers: A Single Autoreactive B Cell Clone Can Drive Autoimmunity

“We observed clonal convergence and selection leading to the predominance of autoreactive V segments in the [wild type]-derived germinal center B cell population, similar to previous observations in autoimmunity and cancer,” they explain. “Serum antibodies displayed epitope spreading, further supported by our finding of [wild type]-derived Ab deposits (IgG2c) in the kidneys of 564Igi mixed chimeras.”

Thus, clonal expansion of wild type B cells in autoreactive germinal centers appeared to be at the heart of epitope spreading and the consequent autoimmune response. Even more importantly, researchers concluded that “self-reactive 564Igi B cells are sufficient to break tolerance and induce the formation of autoreactive [germinal centers], which are predominantly composed of [wild type]-derived cells.”

Reference

1. Degn SE, van der Poel CE, Firl DJ, et al. Clonal evolution of autoreactive germinal centers. Cell. 2017 Aug 24;170(5):913-926.e19. doi: 10.1016/j.cell.2017.07.026.