Ultrastructural study of highly enriched follicular dendritic cells reveals their morphology and the periodicity of immune complex binding

Abstract

Follicular dendritic cells (FDCs) are immune accessory cells found in the follicles of secondary lymphoid organs where they promote B cell maturation in germinal centers (GCs) that develop following antigen exposure. Recently, we published a method for isolating functional murine FDCs in high purity. We reasoned that disruption of FDC reticula in vivo would alter FDC morphology. The present study was undertaken to determine the morphological features of isolated FDCs. FDC-M1 and immune complex (IC) labeling were used to identify FDCs in isolated preparations. Results at the light-microscopic level revealed that isolated FDCs trapped ICs, expressed FDC-M1 and cadherins, but generally appeared non-dendritic. However, at the ultrastructural level, the majority of FDCs exhibited dendrites and typical euchromatic nuclei that appeared as single, bilobed, or double nuclei. Based on morphology, four varieties of FDCs were distinguishable, possibly indicative of differences in maturity. Remarkably, ICs trapped by FDCs showed a distinctive periodic arrangement consistent with that known to induce immune responses by thymus independent-2 (TI-2) antigens that engage and cross-link multiple B cell receptors. The ability of FDCs to trap ICs and then display these T-cell-dependent antigens with repeating periodicity suggests that multiple B cell receptors are cross-linked by antigen on FDCs, thus promoting B cell stimulation and proliferation. Rapid proliferation is characteristic of the GC reaction, and the arrangement of T-dependent antigens in this periodic fashion may help to explain the profuse B cell proliferation in the GC microenvironment.

T-Independent Antibody Responses to T-Dependent Antigens: A Novel Follicular Dendritic Cell-Dependent Activity

“…The periodicity of ICs on FDCs was reported initially with ICs trapped in vivo (28), followed by similar results in vitro (18). This periodicity of TD Ags in ICs on the surfaces of flexible FDC dendrites with 200 -500 Å spacing corresponds with recurring immunogenic epitopes 95-675 Å apart on a flexible backbone of ideal TI-2 Ags (3,4).…”

“…We were prompted to test this concept after 1) observing TD-Ags in ICs on FDCs periodically spaced 200 -500 Å apart (18,28), which is consistent with recurring epitopes 95-675 Å apart on the flexible backbone of an ideal TI-2 Ag (3, 4), and 2) noting the ability of FDCs to provide BAFF and C4BP, which are known to support TI B cell activation (21)(22)(23)(24)(25)(26). These relationships are illustrated in the model shown in Fig.…”

“…Periodically arranged Ag is thought to provide the first signal, and FDC-Fc␥RIIB appears to be important in periodically arranging ICs such that extensive crosslinking of multiple BCRs can occur (18). As shown in Fig.…”

“…The Ags trapped in ICs on FDCs are typically TD, and these Ags are arranged periodically with characteristic 200 -500 Å spacing on the cell surface (18,28). The periodicity of ICs on FDCs was reported initially with ICs trapped in vivo (28), followed by similar results in vitro (18).…”

Microtubule-associated Protein-2 is a Sensitive Marker of Primary and Metastatic Neuroblastoma

“…FDCs display complex 3-dimensional ultrastructural morphology, including numerous dendritic processes. 18 It is not unreasonable to presume that these processes are similar to neuronal dendrites, in that they are enriched with microtubules to maintain their structure, and require MAP-2 proteins to promote microtubule stability. Lastly, a ''granular pattern'' of cytoplasmic staining is present in a subset of tissue macrophages and cells of the monocyte/macrophage lineage.…”