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ResearchIn-Press PreviewAutoimmunityImmunology Open Access | 10.1172/JCI190106

B cells shape naïve CD8 T cell programming

Cameron Manes,1 Miguel Guerrero Moreno,1 Jennifer Cimons,1 Marc A. D'Antonio,1 Tonya M. Brunetti,1 Michael G. Harbell,1 Sean Selva,2 Christopher Mizenko,2 Tyler L. Borko,2 Erika L. Lasda,3 Jay R. Hesselberth,3 Elena W.Y. Hsieh,1 Michael R. Verneris,4 Amanda L. Piquet,3 Laurent Gapin,1 Ross M. Kedl,1 and Jared Klarquist1

1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

Find articles by Manes, C. in: PubMed | Google Scholar

1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States of America

2Department of Neurology, University of Colorado School of Medicine, Aurora, United States of America

3Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, United States of America

4Department of Pediatrics, Section of Hematology, Oncology, & Bone Marrow Tr, University of Colorado School of Medicine, Aurora, United States of America

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Published April 17, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI190106.
Copyright © 2025, Manes et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 17, 2025 - Version history
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Abstract

The presence of B cells is essential for the formation of CD8 T cell memory after infection and vaccination. In this study, we investigated whether B cells influence the programming of naïve CD8 T cells prior to their involvement in an immune response. RNA sequencing indicated that B cells are necessary for sustaining the FOXO1-controlled transcriptional program, which is critical for their homeostasis. Without an appropriate B cell repertoire, mouse naïve CD8 T cells exhibit a terminal, effector-skewed phenotype, which significantly impacts their response to vaccination. A similar effector-skewed phenotype with reduced FOXO1 expression was observed in naïve CD8 T cells from human patients undergoing B cell-depleting therapies. Furthermore, we show that patients without B cells have a defect in generating long-lived CD8 T cell memory following COVID vaccination. In summary, we demonstrate that B cells promote the quiescence of naïve CD8 T cells, poising them to become memory cells upon vaccination.

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Copyright © 2025 American Society for Clinical Investigation
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Picked up by 4 news outlets
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Posted by 21 X users
Referenced by 4 Bluesky users
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