Aging B Cells are Harmful to Immune Function
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.
Huh! Interesting. It does make intuitive sense that aged dysfunctional B cells could drive CD4+ T-cell dysfunction via maladaptive MHC-II cell-cell interactions. The prominence of Insulin-Receptor signaling in this was surprising but overactive insulin receptor/IGF-1 signaling has been linked to metabolic-driven aging in other cell types/tissue types, so that also makes sense.
I think direct translation to humans will be challenging, given the important role of B-cells in vaccine responses / infection prevention; " Mice were maintained in a pathogen-free, temperature-controlled...environment..." which would not be the typical human lifestyle (other than the historic "boy in the bubble" SCID patients...). Still, *temporary* B-cell ablation (e.g., with anti-CD19 agents) and "micro-replacement" with young HSCs seems like it could be a meaningful longevity-enhancing strategy.