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bioRxiv · 10.1101/2025.08.27.672737

PRDM1 shapes germinal center B-cell clonal diversity by gating chromatin accessibility during light-to-dark zone transition

Vijay, G. M.·Ramaswami, B.·Gierlack, S.·Pease, N. A.·Rothstein, D.·Singh, H.
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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-{kappa}B, 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.

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Vijay, G. M., Ramaswami, B., Gierlack, S., Pease, N. A., Rothstein, D., Singh, H.. 2025-09-01. PRDM1 shapes germinal center B-cell clonal diversity by gating chromatin accessibility during light-to-dark zone transition. https://doi.org/10.1101/2025.08.27.672737

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