Enriched environment and stress exposure influence splenic B lymphocyte composition

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.长期慢性应激对免疫功能具有有害影响，并与诸多不良健康结局相关。脾脏承载了机体约四分之一的淋巴细胞，同时介导固有免疫与适应性免疫应答。然而，对于可对各类应激源产生适应性或适应不良反应的脾脏淋巴细胞亚群，目前尚未明确。本研究针对两种不同饲养环境——标准饲养笼（standard caging, Cntl）与丰富环境饲养（enriched environment, EE）——下的雄性小鼠，探究了不可预知慢性轻度应激（unpredictable chronic mild stress, CMS）暴露对其脾脏组成的影响。丰富环境饲养的小鼠脾细胞绝对数量最高，且在两种饲养环境下，CMS暴露均显著降低了脾细胞数量。以粪便皮质酮代谢物（fecal corticosterone metabolites, FCM）的均值衡量糖皮质激素生成量时，丰富环境饲养小鼠的糖皮质激素生成量显著低于标准饲养笼小鼠。值得注意的是，CMS暴露使丰富环境饲养小鼠的FCM均值升高，但标准饲养笼小鼠的FCM均值未出现显著变化。CMS改变了脾脏内B细胞与T淋巴细胞的比值：在丰富环境饲养小鼠中，CMS降低了B细胞的占比，却升高了T细胞的占比。脾细胞数量与B细胞/T淋巴细胞比值均与FCM均值呈负相关。丰富环境饲养小鼠的未成熟B细胞与生发中心B细胞占比低于标准饲养笼小鼠。在两种饲养环境下，CMS均显著升高了未成熟B细胞与边缘区B细胞的占比，但降低了滤泡B细胞的占比。FCM均值与未成熟B细胞、边缘区B细胞及生发中心B细胞的占比呈正相关，而与滤泡B细胞的占比呈负相关。综上，脾脏免疫细胞——尤其是B淋巴细胞组成——可被饲养环境与应激所调控，或可使小鼠对免疫挑战产生差异化的应答反应。