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Immunity
. 2023 Mar 16;S1074-7613(23)00094-8.
doi: 10.1016/j.immuni.2023.03.001. Online ahead of print.
A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans
Anoma Nellore 1 , Esther Zumaquero 2 , Christopher D Scharer 3 , Christopher F Fucile 4 , Christopher M Tipton 5 , R Glenn King 2 , Tian Mi 3 , Betty Mousseau 2 , John E Bradley 6 , Fen Zhou 2 , Stuti Mutneja 7 , Paul A Goepfert 8 , Jeremy M Boss 3 , Troy D Randall 6 , Ignacio Sanz 5 , Alexander F Rosenberg 9 , Frances E Lund 10
Affiliations
- PMID: 36958335
- DOI: 10.1016/j.immuni.2023.03.001
Abstract
Seasonal influenza vaccination elicits hemagglutinin (HA)-specific memory B (Bmem) cells, and although multiple Bmem cell populations have been characterized, considerable heterogeneity exists. We found that HA-specific human Bmem cells differed in the expression of surface marker FcRL5 and transcriptional factor T-bet. FcRL5+T-bet+ Bmem cells were transcriptionally similar to effector-like memory cells, while T-betnegFcRL5neg Bmem cells exhibited stem-like central memory properties. FcRL5+ Bmem cells did not express plasma-cell-commitment factors but did express transcriptional, epigenetic, metabolic, and functional programs that poised these cells for antibody production. Accordingly, HA+ T-bet+ Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5+ Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet+ Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet+ Bmem cells were represented in the secondary ASC response to repeat vaccination, suggesting that this effector-like population predicts influenza vaccine durability and recall potential.
Keywords: T-bet; durable immunity; influenza vaccination; memory B cells; plasmablasts.