Work

Effects of stress on thymic B cells in C57BL/6J mice: phenotypic characterization and mechanistic insights

Year: 2026

Type: article

Abstract: Introduction As an important cause of immune system dysfunction, stress can damage thymic stromal cells, leading to a persistent imbalance in thymic function. Thymic B cells can present autoantigens, playing a critical role in the establishment of central T cell tolerance. However, current research on the effects of stress on thymic B cells remains limited. Methods Publicly available scRNA-seq datasets were analyzed to characterize thymic B cell phenotypes and glucocorticoid responsiveness. A restraint stress mouse model was employed to assess stress-induced changes in thymic B cell abundance and phenotype by flow cytometry and histopathology, and transcriptomic alterations by bulk RNA sequencing of sorted thymic B cells. Results Thymic B cells exhibited a distinctive memory B cell signature with constitutively activated immune-related pathways, and robust glucocorticoid responsiveness. Restraint stress significantly reduced thymic B cell numbers, increased the proportion of IgD + IgM + B cells, and downregulated the expression of CD80 and CD86 in IgD + IgM + B cells. Transcriptomic profiling revealed that stress suppressed cell cycle and G2/M checkpoint pathway, inhibited CD40L- and IFN-λ-responsive gene expression, attenuated Aire-dependent gene expression, and diminished the presentation of autoantigens. Furthermore, the expression levels of CD40 and MHC II in most of the thymic B cell subsets were markedly decreased. Discussion This study reveals the detrimental impact of stress on thymic B cell. Collectively, stress impairs thymic B cell proliferation and attenuates critical licensing signals, including the CD40L–CD40 and IFN-λ signaling, thereby leading to a reduction in thymic B cell numbers, compromised activation, and impaired antigen-presenting capacity.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1963346

Authors: Longda Ma, Weibo Shi, Songjun Wang, Bin Cong

Institution: Hebei Medical University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801