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T cell help awakens embryonic stem-like programs in germinal center B-cells

GSE298473 Mus musculus Expression profiling by high throughput sequencing 5 samples Submitted 2025/10/29 Platform GPL24247
Summary
True stem-like phenotypic plasticity is gradually lost during cellular differentiation due to the strengthening of epigenetic barriers. Here, we describe an unprecedented physiological gain of stem-like plasticity in germinal center B cells, that we termed “anaplasis”. Anaplasis was strictly dependent on help from T follicular helper cells and restricted to germinal center (GC) but not activated B cells, indicating both non- and cell-autonomous contributions to this phenotype. Anaplasis involved the transient reactivation of embryonic stem cell programs by T cell-responsive germinal center B cell transcription factors, suggesting an immunological functional checkpoint, that we show can be hijacked and even bypassed by specific lymphoma mutations. Anaplasis signatures were associated with unfavorable outcomes in B cell lymphomas, suggesting their contribution to tumor fitness. Altogether, we document a physiological re-acquisition of stem-like plasticity in germinal center B cells, which co-evolved with non cell-autonomous checkpoints linked to immune selection processes.
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Also filed as BioProject PRJNA1269511 and SRA study SRP588585. Searching any of these in the dataset finder brings you back here.

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