A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans

Anoma Nellore; Esther Zumaquero; Christopher D Scharer; Christopher F Fucile; Christopher M Tipton; R Glenn King; Tian Mi; Betty Mousseau; John E Bradley; Fen Zhou; Stuti Mutneja; Paul A Goepfert; Jeremy M Boss; Troy D Randall; Ignacio Sanz; Alexander F Rosenberg; Frances E Lund

doi:10.1016/j.immuni.2023.03.001

A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans

Immunity. 2023 Apr 11;56(4):847-863.e8. doi: 10.1016/j.immuni.2023.03.001. Epub 2023 Mar 22.

Authors

Anoma Nellore¹, Esther Zumaquero², Christopher D Scharer³, Christopher F Fucile⁴, Christopher M Tipton⁵, R Glenn King², Tian Mi³, Betty Mousseau², John E Bradley⁶, Fen Zhou², Stuti Mutneja⁷, Paul A Goepfert⁸, Jeremy M Boss³, Troy D Randall⁶, Ignacio Sanz⁵, Alexander F Rosenberg⁹, Frances E Lund¹⁰

Affiliations

¹ Department of Medicine, Division of Infectious Disease, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: anellore@uabmc.edu.
² Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
³ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁴ Informatics Institute, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁵ Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁶ Department of Medicine, Division of Clinical Immunology and Rheumatology at The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁷ Department of Medicine, Division of Infectious Disease, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; ImmuneID, Waltham, MA 02451, USA.
⁸ Department of Medicine, Division of Infectious Disease, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁹ Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Informatics Institute, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
¹⁰ Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: flund@uab.edu.

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-bet^negFcRL5^neg 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
Antibody Formation
Humans
Immunologic Memory
Influenza Vaccines*
Influenza, Human* / prevention & control
Memory B Cells
Vaccination

Substances

Influenza Vaccines
Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding