RANKL Induces Organized Lymph Node Growth by Stromal Cell Proliferation

The study demonstrated that mice transgenic for Rank in hair follicles exhibited significant postnatal growth of skin-draining lymph nodes, with an increase in B cell follicles but maintained proportions of other stromal cells. Overproduction of soluble RANKL from transgenic hair follicles led to this growth, and its neutralization normalized lymph node size and B cell follicle numbers. Reticular fibroblastic and vascular stromal cells, which are crucial for lymphoid organ formation, expressed RANK and proliferated excessively, a process halted by RANKL neutralization. These cells also showed elevated levels of CXCL13 and CCL19 chemokines and adhesion molecules MAdCAM-1 and VCAM-1. The findings underscored the role of tissue-derived signals in lymphoid organ homeostasis and identified RANKL as a critical regulator of immune system plasticity.