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Publication : Transcription factor T-bet regulates the maintenance and differentiation potential of lymph node and lung effector memory B cell subsets.

First Author  Risley CA Year  2025
Journal  Immunity Volume  58
Issue  7 Pages  1706-1724.e6
PubMed ID  40543512 Mgi Jnum  J:370806
Mgi Id  MGI:8222361 Doi  10.1016/j.immuni.2025.05.021
Citation  Risley CA, et al. (2025) Transcription factor T-bet regulates the maintenance and differentiation potential of lymph node and lung effector memory B cell subsets. Immunity 58(7):1706-1724.e6
abstractText  While human and mouse memory B cells (MBCs) can express the transcription factor T-bet, its role in regulating MBC function remains unclear. We characterized multiple transcriptionally distinct clusters of mature, somatically mutated nucleoprotein (NP)-specific MBCs in lymph nodes (LNs) and lungs of influenza-infected mice. Although none of the MBCs expressed the plasma cell (PC) lineage commitment factor Blimp1, one cluster was enriched for Tbx21(+) cells. Similar to the previously described human T-bet(+) effector MBC (eMBC) population, Tbx21(+) mouse MBCs upregulated gene networks associated with effector metabolism, protein synthesis, and the unfolded protein response. Constitutive and inducible ablation of T-bet in murine B cells showed that T-bet expression by MBCs was required for persistence of LN and lung eMBCs with rapid in vitro and in vivo PC differentiation potential. Thus, T-bet marks NP(+) eMBCs that are poised to differentiate, and it regulates maintenance of lung-resident MBCs and local PC responses following virus re-exposure.
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