Lymph nodes are connected to the tissues from which they drain via the afferent lymphatics, which transport cells and soluble factors in a unidirectional manner from the tissues to the lymph nodes. Included in this are migratory DCs, which capture antigen in the tissue before trafficking via the afferent lymphatics to the lymph nodes, driven along a chemoattractant chemokine gradient. Once in the lymph node, these migratory DCs can either present antigen and condition naive lymphocytes themselves or, alternatively, transfer antigen to lymph-node-resident DC populations, which in turn engage in antigen presentation to lymphocytes. DCs and circulating T cells, which gain entry to lymph nodes via high endothelial venules (HEVs) are typically found in the space between B cell follicles, known as the interfollicular area. Compartmentalization within B cell follicles separates dark zone B cells from Tfh cells and FDCs present in the light zone. These FDCs, in concert with Tfh cells, coordinate GC reactions, thereby facilitating the processes of class switch recombination and affinity maturation. Effector cells, including antibody-secreting plasma cells and effector T cells, exit the lymph node via the efferent lymphatics, from where they can enter the circulation or home to sites of infection, where some cells will become tissue resident as determined by signals they receive from the activating APC during priming in the lymph node.