RT Journal Article SR Electronic T1 Fcrl5 and T-bet define influenza-specific memory B cells that predict long-lived antibody responses JF bioRxiv FD Cold Spring Harbor Laboratory SP 643973 DO 10.1101/643973 A1 Anoma Nellore A1 Christopher D. Scharer A1 Rodney G. King A1 Christopher M. Tipton A1 Esther Zumaquero A1 Christopher Fucile A1 Betty Mousseau A1 John E. Bradley A1 Kevin Macon A1 Tian Mi A1 Paul A. Goepfert A1 John F. Kearney A1 Jeremy M. Boss A1 Troy D. Randall A1 Ignacio Sanz A1 Alexander Rosenberg A1 Frances E. Lund YR 2019 UL http://biorxiv.org/content/early/2019/05/20/643973.abstract AB Early surrogates for long-lived immunity after inactivated influenza vaccination (IIV) are lacking. Antigen-specific memory B cells (Bmem) after IIV have been recently identified. We show that the antigen-specific Bmem compartment after IIV is heterogenous and comprises a clonotypically and transcriptionally distinct T-bethi subset that persists in circulation over time after vaccination and exclusively correlates with the long-lived antibody response. We demonstrate that this subset has an effector memory transcriptome and is epigenetically remodeled to facilitate intracellular immunoglobulin production. Finally, via clonal sharing, we show an enriched in vivo ontologic relationship between the secondary plasmablast response that develops after vaccine boost and the T-bethi fraction of the flu-specific Bmem response that forms after initial prime. Collectively, our data identify a novel biomarker of durable humoral immunity after influenza vaccination.