Like T cells, circulating B cells express CCR7, which initially directs them into the lymph node across HEVs. Because they also constitutively express the chemokine receptor CXCR5, they are then attracted to the follicles by the ligand for this receptor, CXCL13. The most likely source of CXCL13 is the FDC, possibly along with other follicular stromal cells. This is reminiscent of the expression of CXCL13 by stromal cells during the formation of the lymph node (Section 9-2). B cells are, in turn, the source of the LT that is required for the development of FDCs, which is reminiscent of LTi cells expressing the LT required to activate stromal cells. The reciprocal dependence of B cells and FDCs, and LTis and stromal cells, illustrates the complex web of interactions that organizes secondary lymphoid tissues. A subset of CD4 T cells called T follicular helper, or TFH, cells can also express CXCR5 following their activation by antigen, allowing them to enter B-cell follicles to participate in the formation of germinal centers (see Chapter 10).
9-4 Naive T cells migrate through secondary lymphoid tissues, sampling peptide:MHC complexes on dendritic cells.
Naive T cells perpetually circulate from the bloodstream into lymph nodes, spleen, and mucosa-associated lymphoid tissues and back to the blood (see Fig. 1.21). This allows them to contact thousands of dendritic cells every day and sample the peptide:MHC complexes on the surfaces of these cells. Because of their high rates of recirculation and their concentration in T-cell zones where incoming dendritic cells dwell, each T cell has a high probability of encountering antigens derived from any pathogen that has set up an infection anywhere in the body (Fig. 9.4). Within hours of their arrival, naive T cells that do not encounter their specific antigen exit from the lymphoid tissue and reenter the bloodstream, where they continue to recirculate—via the efferent lymphatics in lymph nodes or MALTs, or directly back to the blood in the spleen, which has no connection with the lymphatic system.
When a naive T cell recognizes its specific antigen on the surface of an activated dendritic cell, however, it ceases to migrate. It remains in the T-cell zone,
Fig. 9.4 Naive T cells encounter antigen during their recirculation through peripheral lymphoid organs. naive T cells recirculate through peripheral lymphoid organs, such as a lymph node (shown here), entering from the arterial blood via the specialized vascular endothelium of high endothelial venules (hevs). entry into the lymph node is regulated by chemokines (not shown) that direct the T cells’ migration through the hev wall and into the paracortical areas, where the T cells encounter mature dendritic cells (top panel). Those T cells shown in green do not encounter their specific antigen; they receive a survival signal through their interaction with self peptide:self MhC complexes and IL-7, and leave the lymph node through the lymphatics to return to the circulation (second panel). T cells shown in blue encounter their specific antigen on the surface of mature dendritic cells; they lose their ability to exit from the node and become activated to proliferate and to differentiate into effector T cells (third panel). after several days, these antigen-specific effector T cells regain the expression of receptors needed to exit from the node, leave via the efferent lymphatics, and enter the circulation in greatly increased numbers (bottom panel).
20 4 6 8 Emigration of effector T cells Time after viral infection (days) Antigen-speciÿc T cells are detained transiently in the lymph node, where they become activated ActivationTrapping Number of antigen-speciÿc cells in efferent lymph