Advisory Committee Chair
Advisory Committee Members
Frances E Lund
Paul A Goepfert
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.
Risley, Christopher A., "T-BET Regulates the Maintenance and ASC Differentiation Potential of the Lymph Node and Lung Memory B Cell Compartments" (2023). All ETDs from UAB. 382.
Available for download on Sunday, September 01, 2024