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T-bet regulates the maintenance and ASC differentiation potential of lymph node and lung effector memory B cell subsets

ABSTRACT: While human and mouse memory B cells (Bmem) can express T-bet, its role in regulating Bmem function is largely unknown. We characterized multiple transcriptionally distinct clusters of mature, somatically-mutated nucleoprotein (NP)-specific Bmem in LNs and lungs of influenza-infected mice. Although none of the Bmem expressed the plasma cell (PC) lineage commitment factors Blimp1, one cluster was enriched for Tbx21+ cells. Like the previously described human T-bet+ effector Bmem (eBmem) population, Tbx21+ mouse Bmem upregulated gene networks associated with effector metabolism, protein synthesis and the unfolded protein response. Using constitutive and inducible mouse models to ablate T-bet in B cells, we showed that T-bet expression by Bmem was required for persistence of LN and lung eBmem with rapid in vitro and in vivo PC differentiation potential. Thus, T-bet marked NP+ eBmem that were poised to differentiate and was required for maintenance of eBmem that respond in the lung following viral re-exposure.

ORGANISM(S): Mus musculus

PROVIDER: GSE288942 | GEO | 2025/06/18

REPOSITORIES: GEO

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The Transcription Factor T-bet Is Induced by Multiple Pathways and Prevents an Endogenous Th2 Cell Program during Th1 Cell Responses

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