Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection

IntroductionUpon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well under...

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Main Authors: Lisan H. Kuijper, Christine Kreher, George Elias, Mathieu Claireaux, Gius Kerster, Amélie V. Bos, Mariël C. Duurland, Veronique A. L. Konijn, Alberta G. A. Paul, Nina de Jong, Rivka de Jongh, Maurice Steenhuis, Juan J. Garcia-Vallejo, Marit J. van Gils, Taco W. Kuijpers, Filip Eftimov, Theo Rispens, C. Ellen van der Schoot, S. Marieke van Ham, Anja ten Brinke
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Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505719/full
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author Lisan H. Kuijper
Christine Kreher
George Elias
Mathieu Claireaux
Mathieu Claireaux
Gius Kerster
Gius Kerster
Amélie V. Bos
Mariël C. Duurland
Veronique A. L. Konijn
Alberta G. A. Paul
Alberta G. A. Paul
Nina de Jong
Rivka de Jongh
Maurice Steenhuis
Juan J. Garcia-Vallejo
Marit J. van Gils
Marit J. van Gils
Taco W. Kuijpers
Filip Eftimov
Theo Rispens
C. Ellen van der Schoot
S. Marieke van Ham
S. Marieke van Ham
Anja ten Brinke
author_facet Lisan H. Kuijper
Christine Kreher
George Elias
Mathieu Claireaux
Mathieu Claireaux
Gius Kerster
Gius Kerster
Amélie V. Bos
Mariël C. Duurland
Veronique A. L. Konijn
Alberta G. A. Paul
Alberta G. A. Paul
Nina de Jong
Rivka de Jongh
Maurice Steenhuis
Juan J. Garcia-Vallejo
Marit J. van Gils
Marit J. van Gils
Taco W. Kuijpers
Filip Eftimov
Theo Rispens
C. Ellen van der Schoot
S. Marieke van Ham
S. Marieke van Ham
Anja ten Brinke
author_sort Lisan H. Kuijper
collection DOAJ
description IntroductionUpon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.MethodIn this study, convalescent individuals with stable RBD antibody levels (n=14, “sustainers”) were compared with donors (n=13) with the greatest antibody decline from a cohort of 132. To investigate the role of the cellular immune compartment in the maintenance of antibody levels, SARS-CoV-2-specific responses at 4 to 6 weeks post-mild COVID-19 infection were characterized using deep immune profiling.ResultsBoth groups had similar frequencies of total SARS-CoV-2-specific B and CD4+ T cells. Sustainers had fewer Spike-specific IgG+ memory B cells early after infection and increased neutralizing capacity of RBD antibodies over time, unlike the declining group. However, declining IgG titers correlated with lower frequency of Spike-specific CD4+ T cells.ConclusionThese data suggest that “sustainers” have unique dynamics of GC reactions, yield different outputs of terminally differentiating cells, and improve the quality of protective antibodies over time. This study helps identify factors controlling formation of long-lived PC and sustained antibody responses.
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series Frontiers in Immunology
spelling doaj-art-1349c4d52dde48a7affaa88e9ae92f482024-12-17T12:10:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15057191505719Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infectionLisan H. Kuijper0Christine Kreher1George Elias2Mathieu Claireaux3Mathieu Claireaux4Gius Kerster5Gius Kerster6Amélie V. Bos7Mariël C. Duurland8Veronique A. L. Konijn9Alberta G. A. Paul10Alberta G. A. Paul11Nina de Jong12Rivka de Jongh13Maurice Steenhuis14Juan J. Garcia-Vallejo15Marit J. van Gils16Marit J. van Gils17Taco W. Kuijpers18Filip Eftimov19Theo Rispens20C. Ellen van der Schoot21S. Marieke van Ham22S. Marieke van Ham23Anja ten Brinke24Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, NetherlandsDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, NetherlandsDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsCytek Biosciences, Inc., Fremont, CA, United StatesDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity and Cancer Center Amsterdam, Amsterdam University Medical Centers, Free University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity and Cancer Center Amsterdam, Amsterdam University Medical Centers, Free University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, NetherlandsDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsDepartment of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Neurology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSwammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsIntroductionUpon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.MethodIn this study, convalescent individuals with stable RBD antibody levels (n=14, “sustainers”) were compared with donors (n=13) with the greatest antibody decline from a cohort of 132. To investigate the role of the cellular immune compartment in the maintenance of antibody levels, SARS-CoV-2-specific responses at 4 to 6 weeks post-mild COVID-19 infection were characterized using deep immune profiling.ResultsBoth groups had similar frequencies of total SARS-CoV-2-specific B and CD4+ T cells. Sustainers had fewer Spike-specific IgG+ memory B cells early after infection and increased neutralizing capacity of RBD antibodies over time, unlike the declining group. However, declining IgG titers correlated with lower frequency of Spike-specific CD4+ T cells.ConclusionThese data suggest that “sustainers” have unique dynamics of GC reactions, yield different outputs of terminally differentiating cells, and improve the quality of protective antibodies over time. This study helps identify factors controlling formation of long-lived PC and sustained antibody responses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505719/fulldeclining/sustained antibody titersdeep-phenotypingSARS-CoV-2CD4+ T cellsneutralization
spellingShingle Lisan H. Kuijper
Christine Kreher
George Elias
Mathieu Claireaux
Mathieu Claireaux
Gius Kerster
Gius Kerster
Amélie V. Bos
Mariël C. Duurland
Veronique A. L. Konijn
Alberta G. A. Paul
Alberta G. A. Paul
Nina de Jong
Rivka de Jongh
Maurice Steenhuis
Juan J. Garcia-Vallejo
Marit J. van Gils
Marit J. van Gils
Taco W. Kuijpers
Filip Eftimov
Theo Rispens
C. Ellen van der Schoot
S. Marieke van Ham
S. Marieke van Ham
Anja ten Brinke
Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
Frontiers in Immunology
declining/sustained antibody titers
deep-phenotyping
SARS-CoV-2
CD4+ T cells
neutralization
title Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
title_full Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
title_fullStr Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
title_full_unstemmed Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
title_short Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection
title_sort longevity of antibody responses is associated with distinct antigen specific b cell subsets early after infection
topic declining/sustained antibody titers
deep-phenotyping
SARS-CoV-2
CD4+ T cells
neutralization
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505719/full
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