Abstract
Germinal-center (GC) B-cell responses are defined by many positive regulators of affinity maturation, but few components that restrain clonal dominance, notably Nr4a1 , are known. We reveal an unsuspected role for PRDM1 (BLIMP1), a plasma-cell determinant, as a feedback regulator of affinity maturation. Single cell RNA-seq and BCR-seq showed that B- cell-specific Prdm1 loss drives an exaggerated GC reaction with larger clones, increased somatic hypermutation, and greater clonal dominance, independent of Nr4a1 . Single cell chromatin profiling with base-resolution modelling indicated that PRDM1 represses expression of BCR-signaling genes and gates chromatin accessibility at ISRE, EICE, NF-κB, and POU (Oct) motifs. In the absence of PRDM1, enhanced engagement of signaling-inducible transcription factors promotes G1-S transition during light-zone (LZ) selection and fuels dark-zone (DZ) expansion. Thus, PRDM1 attenuates BCR signaling and constrains the LZ→DZ transition, fine-tuning clonal competition thereby maintaining repertoire diversity. The chromatin-encoded checkpoint could be leveraged to modulate vaccine responses.