Abstract
Prolonged chronic stress has deleterious effects on immune function and is associated with numerous negative health outcomes. The spleen harbors one-fourth of the body’s lymphocytes and mediates both innate and adaptive immune responses. However, the subset of splenic lymphocytes that respond, either adaptively or maladaptively, to various stressors remains largely unknown. Here we investigated the effects of unpredictable chronic mild stress (CMS) exposure on spleen composition in male mice housed in two different caging conditions: standard caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest absolute number of splenocytes and CMS exposure significantly lowered splenocyte numbers in both caging conditions. Glucocorticoid production, measured by mean fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS markedly increased the frequency of immature and marginal zone B cells, but decreased the frequency of follicular B cells in both caging conditions. Mean FCM correlated positively with frequency of immature, marginal zone and germinal center B cells, but negatively with frequency of follicular B cells. To conclude, splenic immune cells, particularly B lymphocyte composition, are modulated by caging environment and stress and may prime mice differently to respond to immune challenges.
Highlights
The spleen serves as a hematopoietic and secondary lymphoid organ in mice
We investigated whether standard (Cntl)- and EE-caged mice with and without unpredictable chronic mild stress (CMS) exhibited differences in spleen composition and we determined the relationship between the magnitude of HPA activation (as determined by mean fecal corticosterone metabolites (FCM)) and splenocyte subpopulations
GC receptors (GRs) expression was assessed in immune cell subsets following standard gating of the time parameter, single cell lymphocytes expressing CD45
Summary
The spleen serves as a hematopoietic and secondary lymphoid organ in mice. It is comprised of two morphologically and functionally distinct regions: the white (marginal zone) and the red pulp. Lymphocytes and macrophages traffic through and plasma cell formation occurs upon antigen stimulation. Mature B cells recirculating through the spleen are known as follicular B cells. As follicles are adjacent to T cell zones, this proximity allows for follicular B cells to participate in antigen-induced T cell-dependent responses [1]. The marginal zone B cells express high CD21 levels and allow for presentation of pathogenic lipid antigens to invariant NK cells (iNKC) and primarily mediate T cell-independent responses to blood-born pathogens [1]
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