ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Autonomic Neuroscience
This article is part of the Research TopicMind-Body Networks: Structural, Functional, and Metabolic Processes in Central-Autonomic Regulation in Health and DiseaseView all 3 articles
Immune-Derived Cardiac Autonomic Signatures: Predicting Autonomic Responses to Exercise from B-Cell Phenotypes
Provisionally accepted
Matías Castillo-Aguilar1,2
Ginés Viscor3
Lindybeth Sarmiento Varón1,2
Julieta Sepúlveda-Yañez1,4
Marcelo A Navarrete1,2
Cristian Núñez-Espinosa1,2,5*- 1Centro Asistencial Docente y de Investigación (CADI-UMAG), Punta Arenas, Chile
- 2Escuela de Medicina, Universidad de Magallanes (UMAG), Punta Arenas, Chile
- 3Physiology Section, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
- 4Facultad de Ciencias de la Salud, Universidad de Magallanes (UMAG), Punta Arenas, Chile
- 5University of Magallanes, Punta Arenas, Chile
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Objective: 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. Material and Methods: 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 five-minute 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. Results: 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. Conclusion: 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.
Keywords: Aging, Autonomic Nervous System, B cells, Exercise, Heart rate variability, immunosenescence
Received: 10 Sep 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 Castillo-Aguilar, Viscor, Sarmiento Varón, Sepúlveda-Yañez, Navarrete and Núñez-Espinosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cristian Núñez-Espinosa
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