Hyaluronan Accumulates in Inflamed Lymph Nodes and Promotes B-Cell Activation

The extracellular matrix component hyaluronan (HA) plays important roles in inflammation and immune regulation. However, its involvement in lymphoid tissue during autoreactive processes remains poorly understood. Here, using the DORmO mouse model of autoimmune diabetes, we demonstrate that HA progressively accumulates in lymph nodes and splenic germinal centers during disease development. This accumulation is accompanied by a shift from high to low molecular mass HA fragments. Through immunofluorescence microscopy, we observed extensive colocalization between HA deposits and B cells in germinal centers. Inhibition of HA synthesis using 4-methylumbelliferone (4-MU) increased lymph node stiffness. Treatment with 4-MU decreased immunoglobulin production and reduced B cell activation and differentiation into plasmablasts following immunization. These findings reveal a previously unrecognized role for HA in regulating B cell responses within lymphoid tissues during autoimmune reactions and suggest that targeting HA synthesis may represent a novel therapeutic strategy for conditions involving dysregulated B cell responses.