ORF28-02 - Chronic Growth Hormone Excess Drives Premature Immune Aging by Reshaping Splenic Architecture and B Cell Subsets

Aging is accompanied by progressive immune remodeling, including cellular and structural alterations within secondary lymphoid organs. Excess growth hormone (GH) action accelerates organismal aging; however, its effects on the immune system, particularly age-associated B-cell remodeling and splenic architecture, remain poorly defined, despite higher GH receptor expression in B cells compared with other immune cell populations. The objective of this study was to determine whether chronic GH excess accelerates age-related changes in splenic morphology and B cell subset composition in spleen and bone marrow. Thirteen-month-old male and female bovine GH transgenic (bGH) mice and age-matched wild-type (WT) controls were analyzed. Spleens were bisected; one half was processed for histological analysis, while the other half was used to prepare single-cell suspensions, followed by monoclonal antibody staining and multicolor flow cytometric analysis. B-cell subsets follicular (FO; CD21⁻CD23⁺), marginal zone (MZ; CD21⁺CD23⁻), and age-associated B cells (ABCs; CD21⁻CD23⁻) were quantified by multicolor flow cytometry. Splenic white and red pulp areas were quantified from hematoxylin and eosin-stained sections using QuPath to assess white pulp (WP) and red pulp (RP) composition. Statistical comparisons of B-cell subsets were performed using two-way ANOVA in GraphPad Prism. Compared with WT controls, aged bGH mice exhibited a significant reduction in splenic white pulp, accompanied by reciprocal expansion of red pulp. Expanded red pulp in bGH mice showed increased infiltration of macrophages and megakaryocytes, along with evidence of erythroid hyperplasia. In addition, flow-cytometric analysis revealed an age-dependent accumulation of pro-inflammatory ABCs at the expense of naïve FO B cells in both spleen and bone marrow. Together, these findings demonstrate that excess GH action accelerates immune aging by coupling splenic architectural remodeling with skewing of B-cell populations toward an age-associated proinflammatory phenotype. Given that GH signaling is pharmacologically targetable, these data support GH antagonism (Pegvisomant; an FDA-approved drug) as a potential strategy to preserve immune healthspan during aging.

Acknowledgments: This work is supported in part by the NIH grant AG059779, P30AG13319, and the State of Ohio’s Eminent Scholar Program includes a gift from Milton and Lawrence Goll

Targeted Conference: ENDO Annual Meeting to be held in Chicago, Illinois, USA, from June 13 to June 16, 2026.