Fig. 10.4 T cells and B cells must recognize antigens contained within the same molecular complex in order to interact. In this example, an internal viral protein harbors a peptide epitope (shown as red) that is presented by MHC class II molecules and is recognized by a CD4 T cell. The virus also harbors a native epitope on an external viral coat protein (shown as blue) that is recognized by the surface immunoglobulin on a B cell. If the virus is captured and presented by a dendritic cell, a peptide-specific CD4 T cell (blue) becomes activated (top left panel), whereas nonspecific T cells (green) remain inactive. If the virus is recognized by a specific B cell (top right panel), peptides derived from internal viral proteins are processed and presented by MHC class II molecules. When the activated T cell recognizes its peptide on this B cell (bottom panel), the T cell will deliver various accessory signals to the B cell that promote antibody production against the coat protein. This process is known as linked recognition.
Fig. 10.5 Antigen-binding B cells meet T cells at the border between the T-cell area and a B-cell follicle in secondary lymphoid tissues. Antigens enter the spleen from the blood and collect in T-cell zones and follicles (first panel). Naive CCR7-positive T cells and CXCR5-positive B cells migrate to distinct regions where the chemokines CCL19 and CCL21, or CXCL13 and 7α, 25-hydroxycholesterol (7α, 25-HC), respectively, are being produced (second panel). If a B cell encounters its antigen, either on a follicular dendritic cell (FDC) or a macrophage, it increases expression of CCR7 and migrates toward the border with the T-cell zone (third panel). T cells activated by antigen-presenting dendritic cells induce expression of CXCR5 and migrate to this same border, where linked recognition induces further B-cell proliferation. After 2 to 3 days, B cells reduce expression of CCR7, but retain EBI2 and migrate in response to 7α, 25-HC to the outer follicle and interfollicular regions (fourth panel). After another day or so, some B cells cluster in the interfollicular regions near the red pulp, proliferate, and differentiate into plasmablasts, forming a primary focus with terminal differentiation into antibody-secreting plasma cells. T cells that retain EBI2 expression may remain in the follicle and induce Bcl-6 expression to become TFH cells that participate with B cells there to form a germinal center reaction.