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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE298473 | GEO | 2025/10/29

REPOSITORIES: GEO

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