The follicle provides signals necessary for B-cell survival. In particular, the TNF-family member BAFF (for B-cell activating factor belonging to the TNF family) is made by several cell types, but is produced abundantly by the follicular dendritic cells (FDCs). FDCs are non-hematopoietic cells resident in the B-cell follicles that are specialized to capture antigens for recognition by B-cell antigen receptors (see Section 9-1). B cells express three different receptors for BAFF, namely BAFF-R, BCMA, and TACI. The BAFF-R is the most important for follicular B-cell survival, because mutant mice lacking BAFF-R have mainly immature B cells and few long-lived peripheral B cells. BCMA and TACI also bind the related TNF family cytokine APRIL, which is not required for the survival of immature B cells but is important for IgA antibody production, as we shall see in Chapter 10.
Fig. 8.12 Transitional B cells complete their maturation in B-cell follicles in the spleen. The micrograph in the top panel shows a cross-sectional view of a mouse spleen indicating the distribution of B cells (anti-B220, brown) and T cells (anti-CD3, blue), comprising the white pulp. Surrounding the B-cell-rich follicles (intense brown staining) are the marginal zones (also brown due to presence of B220+ B cells). The white pulp cords sit within the red pulp, which is rich in myeloid cells (mostly macrophages), plasma cells, and passing red blood cells. Transitional B cells that have left the bone marrow must complete their maturation in the B-cell follicles of the spleen, where they receive necessary maturation and survival signals (middle panel). One essential component is a low level of signaling through the B-cell receptor. A second essential factor is the expression of BAFF, a TNF-family member, on follicular dendritic cells (FDCs). BAFF stimulates the BAFF-R on transitional B cells, promoting B-cell survival. Newly emigrated transitional B cells (T1) exhibit high levels of surface IgM, little IgD, and the BAFF-R. In the B-cell follicles, these cells upregulate CD21 to become transitional stage 2 B cells (T2). Finally, the cells upregulate surface IgD, and become long-lived mature B cells. The majority of long-lived B cells are recirculating B cells, known as follicular B cells. A second, less numerous subset is the marginal zone B-cell population. Marginal zone B cells are thought to be weakly self-reactive and express very high levels of the complement receptor CD21. These cells migrate to the marginal zones of the splenic white pulp, an area at the white pulp/red pulp junctions. In this location, marginal zone B cells are poised to make rapid responses to blood-borne antigens or pathogens. Transitional T1 B cells that are excluded from the follicles fail to receive maturation and survival signals and will die within 2–3 days of leaving the bone marrow (bottom panel). Self-reactive anergic B cells are also excluded from the follicles and undergo cell death. Micrograph courtesy of Xiaoming Wang and Jason Cyster. Howard Hughes Medical Institute and Department of Microbiology and Immunology, UCSF.