tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Esther Zumaquero[SUP] 2 [/SUP], Christopher D Scharer[SUP] 3 [/SUP], Christopher F Fucile[SUP] 4 [/SUP], Christopher M Tipton[SUP] 5 [/SUP], R Glenn King[SUP] 2 [/SUP], Tian Mi[SUP] 3 [/SUP], Betty Mousseau[SUP] 2 [/SUP], John E Bradley[SUP] 6 [/SUP], Fen Zhou[SUP] 2 [/SUP], Stuti Mutneja[SUP] 7 [/SUP], Paul A Goepfert[SUP] 8 [/SUP], Jeremy M Boss[SUP] 3 [/SUP], Troy D Randall[SUP] 6 [/SUP], Ignacio Sanz[SUP] 5 [/SUP], Alexander F Rosenberg[SUP] 9 [/SUP], Frances E Lund[SUP] 10 [/SUP]
Affiliations
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[SUP]+[/SUP]T-bet[SUP]+[/SUP] Bmem cells were transcriptionally similar to effector-like memory cells, while T-bet[SUP]neg[/SUP]FcRL5[SUP]neg[/SUP] Bmem cells exhibited stem-like central memory properties. FcRL5[SUP]+[/SUP] 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[SUP]+[/SUP] T-bet[SUP]+[/SUP] Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5[SUP]+[/SUP] Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet[SUP]+[/SUP] Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet[SUP]+[/SUP] 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.
. 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[SUP] 1 [/SUP], Esther Zumaquero[SUP] 2 [/SUP], Christopher D Scharer[SUP] 3 [/SUP], Christopher F Fucile[SUP] 4 [/SUP], Christopher M Tipton[SUP] 5 [/SUP], R Glenn King[SUP] 2 [/SUP], Tian Mi[SUP] 3 [/SUP], Betty Mousseau[SUP] 2 [/SUP], John E Bradley[SUP] 6 [/SUP], Fen Zhou[SUP] 2 [/SUP], Stuti Mutneja[SUP] 7 [/SUP], Paul A Goepfert[SUP] 8 [/SUP], Jeremy M Boss[SUP] 3 [/SUP], Troy D Randall[SUP] 6 [/SUP], Ignacio Sanz[SUP] 5 [/SUP], Alexander F Rosenberg[SUP] 9 [/SUP], Frances E Lund[SUP] 10 [/SUP]
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[SUP]+[/SUP]T-bet[SUP]+[/SUP] Bmem cells were transcriptionally similar to effector-like memory cells, while T-bet[SUP]neg[/SUP]FcRL5[SUP]neg[/SUP] Bmem cells exhibited stem-like central memory properties. FcRL5[SUP]+[/SUP] 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[SUP]+[/SUP] T-bet[SUP]+[/SUP] Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5[SUP]+[/SUP] Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet[SUP]+[/SUP] Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet[SUP]+[/SUP] 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.