Physiologic and pharmacologic role of the glucocorticoid receptor in germinal center B cells and plasmacytic differentiation.

Glucocorticoid receptor (GR) constitutively localizes to the nucleus in germinal center B cells and transcriptionally modulates GC homeostasis and plasmablast differentiation.

• Why it matters: DLBCL derived from GC B cells shows somatic hypermutation that disrupts GR binding in super-enhancers of oncogenes, implying GR is important for normal and malignant GC programs.
• What they did: Using a GC-specific Nr3c1 knockout mouse model plus multi-omics in murine and human GC B cells, they tested baseline GR loss and glucocorticoid pharmacologic dosing.
• The result: Baseline GR activity loss caused mild GC hyperplasia and impaired plasmacytic differentiation, while pharmacologic glucocorticoid doses were preferentially toxic to GC cells in a GC B cell–autonomous manner.

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