Enriched environment and stress exposure influence splenic B lymphocyte composition

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.

Chronic Gestational Inflammation: Transfer of Maternal Adaptation over Two Generations of Progeny

“…Interestingly, the sustained upregulation of leukocyte GR into the second generation of offspring may suggest epigenetic adaptation or primordial germline inheritance adaptation. This is also in line with a previous report with upregulated GR in response to chronic mild psychological stress [45]. In the study by Nephew and colleagues, the hypomethylation of GR gene promotor regions was lost in the second-generation offspring.…”

“…Similar to current data, splenic macrophages previously displayed insensitivity to glucocorticoids and enhanced IL-6 production in a model of chronic social stress [53]. Although the corticosterone levels were not indicative of glucocorticoid insensitivity in the current study, the modulation of splenic cell composition and GR levels, which was also reported in another model of chronic mild stress [45], suggests a selective GR insensitivity in the splenic macrophages, priming the immune system to a relatively more proinflammatory phenotype.…”

“…For example, in PTSD veterans, lower total leukocyte GR density was reported [42], specifically in T-lymphocytes, B-lymphocytes, and NK cells [43]. In contrast, PTSD and anxiety disorders have also been associated with elevated lymphocyte GR expression [44], specifically in neutrophils [45]. This is possibly the result of glucocorticoid adaptation occurring across a continuum where GR levels initially increase in response to acutely increased glucocorticoid levels, followed by GR downregulation when glucocorticoid hypersecretion becomes chronic.…”

Environmental enrichment modulates the response to chronic stress in zebrafish

“…Similarly, a study has recently found that EE during adolescence increased the amount of glucocorticoid receptors in the hippocampus and reduced circulating levels of corticosterone, improving the negative feedback of the neuroendocrine axis in rats from stressed strains (McCreary et al, 2016). At the same time, EE attenuated the increase in corticosterone after alcohol ingestion (Lopez and Laber, 2015) and decreased corticosterone production as measured by fecal corticosterone metabolites in mice (Gurfein et al, 2017). In this context, it is notable that EE influences the neuroendocrine axis and affects the production of glucocorticoids induced by different factors, in agreement with our study.…”

Physiological crosstalk between the Mel1a and Mel1c pathways modulates melatonin-mediated, monochromatic light combination-induced bursa B-lymphocyte proliferation in chickens

“…As a key cell type mediating humoral adaptive immunity, B lymphocytes have rst been described in chickens as antibody-producing cells [22]. Consistent with this essential function, B-lymphocytes development and maturation can be affected by several environmental factors, such as the caging environment [23], heat stress [24], and photoperiod. Here, we constructed a light-color conversion system throughout the growth of chickens to explore the effect of monochromatic lights combinations on Blymphocyte proliferation and bursa development.…”