T zones the primary sites of T and Bcell recruitment into antibody responses

These zones are packed with migrating cells:

1 Interdigitating dendritic cells (IDCs) (Figure 20.11), permeate all parts of this zone. On their surface are processed peptides held in the antigen-presenting grooves of MHC molecules. IDCs enter the T zones of lymph nodes from the intranodal lymphatics. Those in mucosal lymphoid tissues probably come directly from local epithelia. IDCs in the spleen enter via the blood and include cells that have migrated from internal organs.

2 Virgin B and T cells and some memory cells enter the T zone by passing across specialized small blood vessels. In most T zones, these take the form of high endothelial venules that express a series of molecules that have ligands carried by recirculating and newly produced virgin B cells. Interaction between these pairs of molecules causes the lymphocytes to adhere to and

Antigen

Antigen

Dendritic Cell Cell Priming

Figure 20.11 T-cell priming and T-cell-dependent B-cell activation in a lymph node. Local disturbance induces dendritic cells in the tissues to take up material from their surroundings. Ingested proteins are processed to peptides inside the cell (Figure 20.3). Dendritic cells that have taken up antigen migrate through afferent lymphatics to draining lymph nodes or through the blood to the spleen. By the time they reach a T zone, they have differentiated into interdigitating cells, which are specialized at presenting antigenic peptides, held in MHC molecules, to recirculating T cells. Virgin T cells migrating through the T zones move over the surface of the interdigitating cells and are activated if they meet antigen they recognize. As the result of this priming process, they move to the outer T zone and become targets for B cells that have taken up

Figure 20.11 T-cell priming and T-cell-dependent B-cell activation in a lymph node. Local disturbance induces dendritic cells in the tissues to take up material from their surroundings. Ingested proteins are processed to peptides inside the cell (Figure 20.3). Dendritic cells that have taken up antigen migrate through afferent lymphatics to draining lymph nodes or through the blood to the spleen. By the time they reach a T zone, they have differentiated into interdigitating cells, which are specialized at presenting antigenic peptides, held in MHC molecules, to recirculating T cells. Virgin T cells migrating through the T zones move over the surface of the interdigitating cells and are activated if they meet antigen they recognize. As the result of this priming process, they move to the outer T zone and become targets for B cells that have taken up cross the venules into the T zones. Migration of these cells to the T zone in the spleen occurs after adhesion to the marginal zone blood sinusoids.

3 Primed T cells locate towards the edges of the T zones. These cells are very efficient at interacting with B cells that have taken and processed antigen. The primed as opposed to virgin T cells are able to deliver co-stimulatory signals via CD40 and B7.1 and B7.2 to B cells that specifically engage their TCR. B cells activated in this way migrate to extrafollicular foci of B-cell proliferation - the medullary cords in lymph nodes - where they generate short-lived plasma cells. Other B cells migrate to follicles where they may form germinal centres. T cells, after a brief period of proliferation in the T zone, either leave the node as effector cells/recirculating memory T cells or migrate to follicles, where they proliferate further and participate in the selection of B cells that have mutated the Ig variable-region genes in germinal centres (Figure 20.14). The consequences of this cognate T cell-B cell interaction are described in more detail in the text.

up and processed antigens. About one-half of the primed T cells have preformed CD40 ligand in granules in their cytoplasm. The presence of this preformed B-cell coactivation molecule is not characteristically found in recirculating memory T cells. 4 All B-cell types, including marginal zone memory B cells, migrate to the outer T zones if they have taken up and processed antigen. Unlike recirculating B cells, they stay in the outer T zone until they make cognate interaction with a T cell, but those failing to make this encounter die within 3 days.

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