B cells drive CD4 T cell immunosenescence and age-associated health decline

Dysregulation of the adaptive immune system is a key feature of aging and is associated with age-related chronic diseases and mortality. Here, we find that T cell aging, especially in the CD4 subset, is controlled by B cells. B cells contributed to the age-related reduction of naive CD4 T cells, their differentiation toward immunosenescent T cell subsets, and age-associated T cell receptor clonal restriction. Concurrently, mice lacking B cells displayed improvements in health span and life span. We uncovered a role for B cell-intrinsic insulin receptor signaling in influencing age-related B cell phenotypes that in turn induces CD4 T cell dysfunction, a process that is in part driven by major histocompatibility complex class II. These results identify B cells as critical mediators driving age-associated adaptive immune dysfunction and health-span outcomes and suggest previously unrecognized modalities to manage aging and related health decline.

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Publication Details

Journal
Science Immunology
Published
2026-01-30
DOI
https://doi.org/10.1126/sciimmunol.adv7615
Citations
2
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
48.87
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article

B cells drive CD4 T cell immunosenescence and age-associated health decline

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T-cell and B-cell Immunology
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B cells drive CD4 T cell immunosenescence and age-associated health decline

Sue Tsai, Shehnaz Khan, M. Woo, Azin Sayad, Pamela S. Ohashi, D. Furman, Adam J. Gehring, Faisal J. Alibhai, Nan Chen, Mainak Chakraborty, LI Ren-ke, Mansoor Husain, Shawn Winer, Fei Wu, Tao Wang, Yi Tao Chan, Daniel A. Winer
article en
2 citations

Abstract

Dysregulation of the adaptive immune system is a key feature of aging and is associated with age-related chronic diseases and mortality. Here, we find that T cell aging, especially in the CD4 subset, is controlled by B cells. B cells contributed to the age-related reduction of naive CD4 T cells, their differentiation toward immunosenescent T cell subsets, and age-associated T cell receptor clonal restriction. Concurrently, mice lacking B cells displayed improvements in health span and life span. We uncovered a role for B cell-intrinsic insulin receptor signaling in influencing age-related B cell phenotypes that in turn induces CD4 T cell dysfunction, a process that is in part driven by major histocompatibility complex class II. These results identify B cells as critical mediators driving age-associated adaptive immune dysfunction and health-span outcomes and suggest previously unrecognized modalities to manage aging and related health decline.

Science ImmunologyVol. 11(115)
Mount Sinai Hospital (CA), University Health Network (CA), Buck Institute for Research on Aging (US), University of Alberta (CA), University of Toronto (CA), Slovak Academy of Sciences (SK), Discovery Centre (CA), Toronto General Hospital (CA), Princess Margaret Cancer Centre (CA), Ted Rogers Centre for Heart Research (CA), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK), Schwartz/Reisman Emergency Medicine Institute (CA), Krembil Research Institute
Good health and well-being
Openalex Percentile: Top 0%
T-cell and B-cell Immunology
48.87
DOISourceOpenAlex
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