Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor

Follicular regulatory T (T(FR)) cells are a specialized suppressive subset that controls the germinal center (GC) response and maintains humoral self-tolerance. The mechanisms that maintain T(FR) lineage identity and suppressive activity remain largely unknown. Here, we show that expression of Blimp1 by FoxP3(+) T(FR) cells is essential for T(FR) lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in T(FR) cells reduced FoxP3 and CTLA-4 expression and increased pro-inflammatory cytokines and spontaneous production of autoantibodies, including elevated IgE. Maintenance of T(FR) stability reflected Blimp1-dependent repression of the IL-23R-STAT3 axis and activation of the CD25-STAT5 pathway, while silenced IL-23R-STAT3 or increased STAT5 activation rescued the Blimp1-deficient T(FR) phenotype. Blimp1-dependent control of CXCR5/CCR7 expression also regulated T(FR) homing into the GC. These findings uncover a Blimp1-dependent T(FR) checkpoint that enforces suppressive activity and acts as a gatekeeper of GC entry.