T-follicular regulatory cells expand to control germinal center plasma cell output but fail to curb autoreactivity.

ABSTRACT: Autoantibodies generated in germinal centers (GCs) contribute to the pathogenesis of autoimmune diseases. GCs are controlled by specialized FoxP3+ T-follicular regulatory cells (Tfr), but their role in established autoimmunity is unclear. We generated autoimmune bone marrow chimeras in which Tfr could be specifically ablated by diphtheria toxin. Furthermore, we tracked the clonal persistence and evolution of Tfr populations using Confetti reporters. Ablation of Tfr caused increased early plasma cell output, but longer-term ablation did not increase plasma cell levels beyond those of Tfr-sufficient controls, suggesting that Tfr fail to contain chronic autoreactive GC responses. In agreement, Tfr were robustly induced in early autoreactive GCs but then waned. Moreover, we observed polyclonal

SUBMITTER: Fahlquist-Hagert C 

PROVIDER: S-EPMC11417334 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature