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Murine Glucocorticoid Receptors Orchestrate B Cell Migration Selectively between Bone Marrow and Blood
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-22 , DOI: 10.4049/jimmunol.1901135
Derek W Cain 1 , Carl D Bortner 1 , David Diaz-Jimenez 1 , Maria G Petrillo 1 , Amanda Gruver-Yates 1 , John A Cidlowski 2
Affiliation  

Key Points Glucocorticoid binding to glucocorticoid receptors in B cells upregulates CXCR4. Glucocorticoids control diurnal exchange of B cells between blood and bone marrow. B cellGRKO mice exhibit impaired IgG response to T-independent (Type II) Ag. Glucocorticoids promote CXCR4 expression by T cells, monocytes, macrophages, and eosinophils, but it is not known if glucocorticoids regulate CXCR4 in B cells. Considering the important contributions of CXCR4 to B cell development and function, we investigated the glucocorticoid/CXCR4 axis in mice. We demonstrate that glucocorticoids upregulate CXCR4 mRNA and protein in mouse B cells. Using a novel strain of mice lacking glucocorticoid receptors (GRs) specifically in B cells, we show that reduced CXCR4 expression associated with GR deficiency results in impaired homing of mature B cells to bone marrow, whereas migration to other lymphoid tissues is independent of B cell GRs. The exchange of mature B cells between blood and bone marrow is sensitive to small, physiologic changes in glucocorticoid activity, as evidenced by the lack of circadian rhythmicity in GR-deficient B cell counts normally associated with diurnal patterns of glucocorticoid secretion. B cellGRKO mice mounted normal humoral responses to immunizations with T-dependent and T-independent (Type 1) Ags, but Ab responses to a multivalent T-independent (Type 2) Ag were impaired, a surprise finding considering the immunosuppressive properties commonly attributed to glucocorticoids. We propose that endogenous glucocorticoids regulate a dynamic mode of B cell migration specialized for rapid exchange between bone marrow and blood, perhaps as a means to optimize humoral immunity during diurnal periods of activity.

中文翻译:

鼠糖皮质激素受体在骨髓和血液之间选择性地协调 B 细胞迁移

关键点 糖皮质激素与 B 细胞中的糖皮质激素受体结合可上调 CXCR4。糖皮质激素控制血液和骨髓之间 B 细胞的昼夜交换。B cellGRKO 小鼠表现出对 T 非依赖性(II 型)Ag 的 IgG 反应受损。糖皮质激素通过 T 细胞、单核细胞、巨噬细胞和嗜酸性粒细胞促进 CXCR4 表达,但尚不清楚糖皮质激素是否调节 B 细胞中的 CXCR4。考虑到 CXCR4 对 B 细胞发育和功能的重要贡献,我们研究了小鼠的糖皮质激素/CXCR4 轴。我们证明糖皮质激素上调小鼠 B 细胞中的 CXCR4 mRNA 和蛋白质。使用一种在 B 细胞中缺乏糖皮质激素受体 (GRs) 的新型小鼠,我们表明,与 GR 缺陷相关的 CXCR4 表达降低会导致成熟 B 细胞向骨髓的归巢受损,而向其他淋巴组织的迁移与 B 细胞 GR 无关。血液和骨髓之间成熟 B 细胞的交换对糖皮质激素活性的微小生理变化敏感,这可以通过 GR 缺陷 B 细胞计数缺乏昼夜节律性来证明,这通常与糖皮质激素分泌的昼夜模式相关。B cellGRKO 小鼠对 T 依赖性和 T 非依赖性(1 型)Ag 免疫产生正常的体液反应,但对多价 T 非依赖性(2 型)Ag 的抗体反应受损,考虑到通常归因于免疫抑制的特性,这是一个令人惊讶的发现糖皮质激素。
更新日期:2020-06-22
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