B cells shape naive CD8+ T cell programming
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 naive 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 homeostasis of these T cells. Without an appropriate B cell repertoire, mouse naive 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 naive 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 naive CD8+ T cells, poising them to become memory cells upon vaccination.
Authors
- Erika Lasda (ORCID: https://orcid.org/0000-0001-5698-8386)
- Michael R. Verneris (ORCID: https://orcid.org/0000-0002-7097-5917)
- Elena W.Y. Hsieh (ORCID: https://orcid.org/0000-0003-3969-6597)
- Tyler L. Borko (ORCID: https://orcid.org/0000-0002-6679-1867)
- Jared Klarquist (ORCID: https://orcid.org/0000-0002-4072-3962)
- Sean Selva
- Laurent Gapin (ORCID: https://orcid.org/0000-0001-9730-5174)
- Jay R. Hesselberth (ORCID: https://orcid.org/0000-0002-6299-179X)
- Tonya M. Brunetti (ORCID: https://orcid.org/0000-0002-2228-2198)
- Christopher Mizenko
- Cameron Manes
- Amanda L. Piquet (ORCID: https://orcid.org/0000-0001-7349-6455)
- Ross M. Kedl (ORCID: https://orcid.org/0000-0002-9065-7895)
- Marc D’Antonio (ORCID: https://orcid.org/0000-0002-4243-7230)
- Jennifer Cimons (ORCID: https://orcid.org/0000-0002-8111-8697)
- Michael Harbell
- Miguel Guerrero Moreno (ORCID: https://orcid.org/0009-0000-5308-0428)
Institutions
- ENT and Allergy (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1172/jci190106
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- National Institutes of Health
- Cancer Center, University of Colorado