Opsonized antigens entering lymph degradative activity of subcapsular macrophages nodes from afferent lymphatics bind subcapsular macrophages also allows antigen to be to the complement receptors on the preserves the antigens transported into the follicle surface of macrophages present in trapped on their surfaces, to become localized on the the subcapsular sinus allowing B cells to surface of follicular follicles (Fig. 10.7). These macrophages seem to retain the antigen on their surface rather than ingesting and degrading it. These antigens can then be sampled and carried by antigen-specific follicular B cells. B cells of any antigen specificity could also acquire antigen from these macrophages via their complement receptors and transport it within the follicle. In the spleen, marginal zone B cells shuttle between that site and the follicle, carrying antigen trapped in the marginal zone for deposition on FDCs. SCS macrophages can also actively function to restrict the dissemination of infection. In mice, infection of these macrophages in lymph nodes by vesicular stomatitis virus (VSV), a relative of rabies virus, triggers the cells to produce interferon and to recruit plasmacytoid dendritic cells (pDCs). Type I interferon produced by pDCs restricts further viral spread, which would otherwise eventually pass on to the central nervous system.
After a naive follicular B cell first encounters specific antigen displayed by FDCs or macrophages, within a few hours it will become positioned in the outer follicles of lymphoid tissue close to the sites where antigen enters the lymph node or spleen. This positioning is orchestrated by the B cell’s expression of a chemokine receptor, EBI2 (GPR183), whose ligands are oxysterols such as 7α, 25-dihydroxycholesterol. The precise source of these ligands is still unclear, but they are abundant in the outer follicular and interfollicular regions. After sampling antigens there for 6 hours to 1 day, the B cell induces expression of CCR7, which functions together with EBI2 to distribute activated B cells along the interface between the B-cell follicle and the T-cell zone, where CCL21 is expressed.
During an immune response, T cells are activated within the T-cell zones by dendritic cells. When naive T cells are activated, some will proliferate, differentiate into effector cells, downregulate expression of S1P1, and exit the lymphoid tissue. However, others will induce expression of CXCR5 and migrate to the border with the B-cell follicle. There, T cells can encounter B cells activated during the same response, increasing the chance that they might recognize linked antigens presented by activated B cells that have recently moved to this location (see Fig. 10.5).
Fig. 10.7 Opsonized antigens are captured and preserved by subcapsular sinus macrophages. Macrophages residing in the lymph node subcapsular sinus (SCS) express complement receptors 1 and 2 (CR1 and CR2, respectively), are poorly endocytic, and have reduced levels of lysosomal enzymes compared with macrophages in the medulla. Opsonized antigen arriving from the afferent lymphatics binds to CR1 and CR2 on the surface of SCS macrophages. Instead of being completely degraded by these macrophages, some antigen is retained on the cell surface, where it can be presented and transferred to the surface of follicular B cells. B cells are then able to transport the antigen into the follicle, where it can be trapped on the surfaces of follicular dendritic cells.