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. FcRL5T-bet Bmem cells were transcriptionally similar to effector-like memory cells, while T-betFcRL5 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.
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http://dx.doi.org/10.1016/j.immuni.2023.03.001 | DOI Listing |
bioRxiv
October 2024
Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA.
The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the immune phylogeny of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors during early childhood.
View Article and Find Full Text PDFJ Allergy Clin Immunol
December 2024
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia; Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Australia; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address:
Background: Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown.
View Article and Find Full Text PDFSci Transl Med
August 2024
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.
View Article and Find Full Text PDFNat Commun
August 2024
Infection, Immunity & Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia.
J Infect
October 2024
Dept. Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia; Allergy, Asthma and Clinical Immunology Service, Alfred Hospital, Melbourne, Victoria, Australia; Dept. Immunology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Electronic address:
Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants.
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