The immune system is full of specific examples of what is known as antagonistic pleiotropy, the evolution of systems that are beneficial in youth but become harmful in old age. B cells serve a useful but not absolutely vital role in the immune system; one can survive without B cells if necessary, at the cost of diminished immune responsiveness. Unfortunately, aging brings a growing population of dysfunctional, harmful age-associated B cells that aggravate loss of immune function and age-related disease more generally. Destruction of B cells is readily achieved in animal models, either temporarily or permanently. Temporary clearance of B cells in mice is beneficial, removing the age-associated B cells and replacing them with more functional B cells, while here researchers show that permanent life-long removal of B cells in mice slows aspects of immune aging and improves late-life health.
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.
Link: https://doi.org/10.1126/sciimmunol.adv7615
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