Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function

Abstract

Follicular dendritic cells (FDCs) were identified decades ago by their ability to retain immune complexes and more recent findings indicate that they are a source of B cell attractants and trophic factors. New imaging studies have shown that B cells closely associate with their dendritic processes during migration. Here we will review the properties of these specialized follicular stromal cells and provide an update on the requirements for their maturation into phenotypically distinct cells within germinal center light and dark zones. We will then discuss current understanding of how they help support the B cell immune response.

Figure 1. Schematic representation of follicular stromal and FDC networks in a primary follicle and in the same area after maturation into a GC-containing secondary follicle

Follicular stromal cells (FSCs) and FDCs are suggested to form a contiguous network. Primary follicle FDC are suggested to undergo maturation into light zone (LZ) and dark zone (DZ) FDC in response to signals that include LT, TNF and immune complexes (IC) as well as still unknown (other) signals. Surface markers that typify the cells are listed along with an indication of their relative abundance. The absence of a marker (−) indicates below the level of detection by conventional immuno-staining procedures. Variable reports in the literature indicated as +/−. *, special note as follows: FcgRIIb+/− indicates functional evidence only; CD23 is present on LZ FDC in only certain GCs; IC-trapping in DZ demonstrated only after in vitro incubation; Fibrinogen associated but not expressed.

Figure 2. FDC marker distribution in GC light and dark zones

Serial 7 μm cryostat sections of a draining peripheral lymph node from a mouse that had been immunized s.c. 14 days earlier with NP-CGG in complete Freund’s adjuvant are shown. Sections were stained with antibodies to the indicated markers. GCs are identified as areas deficient in IgD⁺ B cells and positive for GL7 antibody staining. Note the presence of CD35⁺ FDCs in the dark zone that are negative for the light zone FDC markers CD23, FDC-M2 and FcγRIIb. VCAM-1 staining is observed on tingible body macrophages in addition to FDCs. Scale bar, 100 μm.

Figure 3. FDC-M1 staining of GC light zone FDC and tingible body macrophages (TBM)

Tissue preparation and analysis was as in Figure 2. Scale bar, 50 μm.