Highways, byways and breadcrumbs: directing lymphocyte traffic in the lymph node

The lymph node (LN) is charged with a crucial function in the mammalian immune system: to facilitate physical interactions between extremely rare cells arriving from different tissue compartments. Paramount to carrying out this function is its unique placement at the interface between the blood and lymphatic systems, thus enabling tissue-derived antigen and antigen-presenting cells, especially dendritic cells (DCs) to gather in close proximity to blood-derived antigen-specific motile lymphocytes. A generally held view is that this accumulation of cells, coupled with stochastic migration, is itself sufficient to facilitate a physiologically adequate frequency of cell–cell contacts due to random migration within the confined space of the LN. Based on recent data, we propose an expanded model of LN function in which unique architectural features and chemical signals together provide a means of enhancing otherwise unlikely encounters between sparse DCs and rare antigen-specific lymphocytes.