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A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans. 2023

Anoma Nellore, and Esther Zumaquero, and Christopher D Scharer, and Christopher F Fucile, and Christopher M Tipton, and R Glenn King, and Tian Mi, and Betty Mousseau, and John E Bradley, and Fen Zhou, and Stuti Mutneja, and Paul A Goepfert, and Jeremy M Boss, and Troy D Randall, and Ignacio Sanz, and Alexander F Rosenberg, and Frances E Lund
Department of Medicine, Division of Infectious Disease, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: anellore@uabmc.edu.

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.

UI MeSH Term Description Entries
D007156 Immunologic Memory The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. Immune Memory,Immunological Memory,Memory, Immunologic,Immune Memories,Immunologic Memories,Immunological Memories,Memory, Immune,Memory, Immunological
D007251 Influenza, Human An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia. Grippe,Human Flu,Human Influenza,Influenza in Humans,Influenza,Flu, Human,Human Influenzas,Influenza in Human,Influenzas,Influenzas, Human
D007252 Influenza Vaccines Vaccines used to prevent infection by viruses in the family ORTHOMYXOVIRIDAE. It includes both killed and attenuated vaccines. The composition of the vaccines is changed each year in response to antigenic shifts and changes in prevalence of influenza virus strains. The flu vaccines may be mono- or multi-valent, which contains one or more ALPHAINFLUENZAVIRUS and BETAINFLUENZAVIRUS strains. Flu Vaccine,Influenzavirus Vaccine,Monovalent Influenza Vaccine,Universal Flu Vaccine,Universal Influenza Vaccine,Flu Vaccines,High-Dose Trivalent Influenza Vaccine,Influenza Vaccine,Influenza Virus Vaccine,Influenza Virus Vaccines,Influenzavirus Vaccines,Intranasal Live-Attenuated Influenza Vaccine,LAIV Vaccine,Monovalent Influenza Vaccines,Quadrivalent Influenza Vaccine,Trivalent Influenza Vaccine,Trivalent Live Attenuated Influenza Vaccine,Universal Flu Vaccines,Universal Influenza Vaccines,Flu Vaccine, Universal,High Dose Trivalent Influenza Vaccine,Influenza Vaccine, Monovalent,Influenza Vaccine, Quadrivalent,Influenza Vaccine, Trivalent,Influenza Vaccine, Universal,Intranasal Live Attenuated Influenza Vaccine,Vaccine, Flu,Vaccine, Influenza,Vaccine, Influenza Virus,Vaccine, Influenzavirus,Vaccine, LAIV,Vaccine, Monovalent Influenza,Vaccine, Quadrivalent Influenza,Vaccine, Trivalent Influenza,Virus Vaccine, Influenza
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000091245 Memory B Cells A subset of activated B cells generated in response to primary immune challenge or immunization which are capable of giving rise to antibody-secreting cells upon re-challenge (see IMMUNOLOGIC MEMORY). Memory B cells feature many discrete properties indicative of differentiation through ISOTYPE SWITCHING and/or IMMUNOGLOBULIN SOMATIC HYPERMUTATION for rapid and robust recall of specific antibody responses. Memory B-Lymphocytes,B Cell, Memory,B-Lymphocyte, Memory,B-Lymphocytes, Memory,Memory B Cell,Memory B Lymphocytes,Memory B-Lymphocyte
D000914 Antibodies, Viral Immunoglobulins produced in response to VIRAL ANTIGENS. Viral Antibodies
D000917 Antibody Formation The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS. Antibody Production,Antibody Response,Antibody Responses,Formation, Antibody,Production, Antibody,Response, Antibody,Responses, Antibody
D014611 Vaccination Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. Immunization, Active,Active Immunization,Active Immunizations,Immunizations, Active,Vaccinations

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