The microanatomy of B cell activation

Abstract

The logistic problem of B cell antigen encounter in the lymph node has recently been studied by dynamic imaging using two-photon microscopy. These studies combined with the early studies of antigen transport have yielded a more complete picture of the orchestration of B cell activation in vivo. Here we summarize the recent advances and focus on the specialized macrophages that are critical to this process and the role of B cells themselves as antigen transporting cells.

Figure 1. Microanatomy of the lymph node

Schematic of a lymph node showing the locations for antigen presentation to B cells. 1) Subcapsular region. 2) Lymphoid follicle. 3) T zone (paracortex) in the vicinity of HEVs. Lymph drains in the afferent lymphatic to the subcapsular sinus (SCS) and flows to the medullary sinuses. The lymphoid follicle (orange) is situated beneath the SCS and is traversed by occasional follicular conduits (white). Follicular dendritic cells (FDCs) are brown. The T zone (blue) contains HEVs (red) through which lymphocytes enter the lymph node. The medulla (light brown) contains numerous macrophages and cords of plasma cells. Three general locations of B cell access to antigen are labelled and the table summarizes the kinetics and properties of antigens arriving at these sites.

Figure 2. Dynamics of antigen capture in the lymph node

Schematic showing the fate of opsonized (irregular shape) and non-opsonized (circle) antigens draining in the afferent lymphatics. Within minutes SCS macrophages have sampled some of the opsonized antigen while the bulk of antigens continues on to the medullary sinus. Within hours SCS macrophages have translocated some of the opsonized antigens from the lumen into the follicle whereas medullary macrophages have phagocytosed the remaining antigens. Opsonized antigens are then relayed to B cells for deposition on FDCs within a day where they can persist for weeks. In contrast, the remaining antigens are catabolized by medullary macrophages.

Figure 3. Model for role of B cell antigen transport in the primary antibody response

Cognate B cells (green) acquire antigen from SCS macrophages (light brown) and migrate to the T-B border. Upon receipt of T cell help they differentiate into early plasmablasts and migrate to the medullary cords where they secrete antibodies; alternatively they differentiate into GC B cells. Early antibodies feedback to opsonize incoming antigen and these ICs are relayed by SCS macrophages to non-cognate B cells (blue) that transport them into the GC light zone. These antigen-containing ICs are then available for deposition on FDCs (dark brown) and affinity-based selection of GC B cells to become high affinity plasma cells. FMZ, follicular mantle zone.