All ETDs from UAB

Advisory Committee Chair

Hui Hu

Advisory Committee Members

Frances E Lund

Andre Ballesteros-Tato

Paul A Goepfert

Amy Weinmann

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Although human memory B cells (Bmem), including extrafollicular DN2 cells and CD27+ effector Bmem (eBmem), express T-bet, its role in Bmem biology is not understood. We characterized transcriptionally distinct clusters of mature, somatically mutated nucleoprotein (NP)-specific Bmem in LNs of influenza-infected mice. None of the Bmem expressed plasma cell (PC) lineage commitment factors, but one cluster was significantly enriched for Tbx21+ cells that exhibited a molecular signature similar to the previously described human T-bet+ eBmem. Metabolic reprogramming, protein synthesis and the mTOR-dependent unfolded protein response gene networks were all upregulated in Tbx21+ NP+ mouse Bmem. Using constitutive and inducible models to ablate T-bet in B cells, we show that the persistence of LN and lung Bmem with rapid differentiation potential requires T-bet. Thus, T-bet marks human and mouse Bmem that are metabolically poised to differentiate and contributes to the maintenance of the eBmem compartment that provides early protection following reinfection.

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