IgD発現成熟B細胞はグルココルチコイド誘発細胞死に対して感受性が亢進している

Glucocorticoids (GCs) regulate diverse physiological processes, comprising metabolism, immune responses, stress adaptation, and inflammation. Synthetic GCs are widely used for their powerful anti-inflammatory and immunosuppressive effects, in the treatment of autoimmune diseases, allergies, and inflammation. Here, we investigated the role of the glucocorticoid receptor (GR) in B cell development and survival using both B cell-specific GR-deficient mice and continuous in vivo GR agonist treatments. Deletion of the GR in B cells altered splenic B cell subpopulations, increasing follicular and CD21^lo B cells and leading to the accumulation of IgM^-/IgD^- B cells. In vivo treatment with GR agonists, such as Dexamethasone (Dex) and Prednisolone (Pred), selectively depleted IgD^hi follicular while enriching IgM^hi marginal zone B cells. IgM^hi B cells, which were more resistant to GC-induced cell death, showed an increased expression of IL-10 and genes involved in survival, suggesting a potential regulatory function. In vitro, B cell activation via CpG or lipopolysaccharide (LPS) altered IgM/IgD expression and B cell sensitivity to GR agonists, thereby leading to improved B cell survival and increased plasma cell differentiation. Together, these findings suggest that IgD downregulation and IgM upregulation are critical for B cell survival under GC exposure and that GR agonists promote the enrichment of IgM^hi cells resistant to apoptosis.