Immune-derived cardiac autonomic signatures: predicting autonomic responses to exercise from B-cell phenotypes

Aging affects both immune and autonomic regulation, yet their interaction remains poorly characterized. This study investigated how aging B-cell subpopulations, defined by CD21/CD11c expression, are associated with autonomic nervous system (ANS) dynamics, as measured by heart rate variability (HRV) during exercise in older adults.

In this cross-sectional study, 81 community-dwelling older adults (mean age 70.7 ± 5.8 years) underwent immune flow cytometry profiling of total B cells and four CD21/CD11c phenotypes. Continuous R-R interval (RRi) data were recorded at rest, during a standardized Two-Minute Step Test (TMST), and over a 5-min recovery period. A coupled-logistic RRi-vs-time model capturing each participant's cardiac autonomic signature (CAS) was obtained. Individual parameter estimates were regressed on standardized immune predictors using multivariate Bayesian models adjusted for age, sex and body composition.

Higher counts of CD21⁺CD11c⁺ B cells were associated with elevated baseline RRi (resting vagal tone), an increased exercise-induced RRi drop, and an incomplete post-exercise recovery. Conversely, greater CD21^-CD11c^- B-cell counts were associated with lower resting RRi, a faster sympathetic-driven RRi decrease during exercise, and more complete vagal reactivation during recovery. High posterior probability (>90%) was observed for the aforementioned posterior estimates.

CD21⁺CD11c⁺ and CD21^-CD11c^- aging B-cell subsets display opposite associations with ANS responsiveness to acute exercise, suggesting immunosenescence-linked autonomic modulation on the neuro-immune axis. Distinct B-cell phenotypes may serve as biomarkers of resilience or fragility in aging, supporting personalized interventions to optimize cardiovascular health in aging individuals.