Rothstein, D. | bioRxiv Science

bioRxiv2025

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

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.

immunology↗

bioRxiv2023

Phenology across scales: an intercontinental analysis of leaf-out dates in temperate deciduous tree communities

AimTo quantify the intra-community variability of leaf-out (ICVLo) among dominant trees in temperate deciduous forests, assess its links with specific and phylogenetic diversity, identify its environmental drivers, and deduce its ecological consequences with regard to radiation received and exposure to late frost. LocationEastern North America (ENA) and Europe (EUR). Time period2009-2022 Major taxa studiedTemperate deciduous forest trees. MethodsWe developed an approach to quantify ICVLo through the analysis of RGB images taken from phenological cameras. We related ICVLo to species richness, phylogenetic diversity and environmental conditions. We quantified the intra-community variability of the amount of radiation received and of exposure to late frost. ResultsLeaf-out occurred over a longer time interval in ENA than in EUR. The sensitivity of leaf-out to temperature was identical in both regions (-3.4 days per {degrees}C). The distributions of ICVLo were similar in EUR and ENA forests, despite the latter being more species-rich and phylogenetically diverse. In both regions, cooler conditions and an earlier occurrence of leaf-out resulted in higher ICVLo. ICVLo resulted in a ca. 8% difference of radiation absorption over spring among individual trees. Forest communities in ENA had shorter safety margins as regards the exposure to late frosts, and were actually more frequently exposed to late frosts. Main conclusionsWe conducted the first intercontinental analysis of the variability of leaf-out at the scale of tree communities. North American and European forests showed similar ICVLo, in spite of their differences in terms of species richness and phylogenetic diversity, highlighting the relevance of environmental controls on ICVLo. We quantified two ecological implications of ICVLo (difference in terms of radiation absorption and exposure to late frost), which should be explored in the context of ongoing climate change, which affects trees differently according to their phenological niche.

ecology↗