Dendritic cells prompt endothelial cells (blue) to proliferate (pink) during an immune response.

At the initiation of an immune response, lymph nodes can double in size in a day and can be ten times their original size in five to seven days. Webster and colleagues report on page 1903 that dendritic cells, quite distinct from their function in antigen presentation, stimulate endothelial cell proliferation and vascular growth in the growing lymph node.

Peripheral challenge (such as immunization) induces dendritic cells to mature and migrate to the lymph nodes. But what is their role once there? Dendritic cells are well known for their role in B and T cell lymphocyte stimulation but, surprisingly, Lu's team found that without lymphocytes (in Rag−/− mice) dendritic cells could activate lymph node growth and endothelial cell proliferation almost as effectively.

Vascular endothelial growth factor (VEGF) has been implicated in lymph node growth, and the team found that dendritic cells could increase VEGF levels in the lymph node, again, without the need for lymphocytes. Increased VEGF and increased endothelial cell proliferation required dendritic cell–mediated recruitment of cells from the circulation. Either these recruited cells or other lymph node cells (but not the dendritic cells) are then thought to produce the VEGF. Determining how VEGF levels are up-regulated is the subject of ongoing study.

Enlargement of the lymph nodes is a normal step in combating infection, but it also occurs during autoimmune responses. One possibility for combating lymph node growth during autoimmunity is antiangiogenic drugs, which were developed to combat tumors.