Follicular Dendritic Cells (B Lymphocyte Stimulating)

Abstract

Follicular dendritic cells (FDCs) are found in all secondary lymphoid tissues, where they function as a repository of antigens to maintain long‐term IgG and IgE responses. Antigens are trapped and retained on FDCs in the form of immune complexes; and while most immune complexes require large quantities to induce an immune response, FDC‐trapped antigens are remarkably immunogenic and only a few picogram can induce microgram concentrations of a specific antibody. In addition to providing antigens, FDCs provide a number of additional signals (e.g. BAFF, IL‐6) that further contribute to antibody production. In addition to their contributions to immunity in health, FDCs are involved in some pathological situations including HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome), sarcoma/lymphoma, prion‐mediated transmissible spongiform encephalopathies (e.g. Creutzfeldt–Jakob) and Castleman disease. A further understanding of FDCs and their functions in both health and disease may aid our ability to better regulate immunity and ameliorate some disease states.

Key Concepts

  • FDCs trap antigens as immune complexes that consist of antigen in the presence of either specific antibodies or complement proteins, or both. FDCs trap immune complexes using CD32 and/or CD21.
  • FDC‐trapped antigens or iccosomes are highly immunogenic and minute amounts (picogram) can induce significant quantities (microgram) of a specific antibody.
  • FDC‐trapped antigens remain on the surface of FDCs and are not internalised. These antigens are not degraded but maintain their native configuration and immunoreactivity for many months.
  • In addition to trapping conventional antigens, FDCs also trap HIV (and potentially other viruses) and maintain the infectious nature for many months. FDC‐trapped HIV can transmit infection to adjacent target cells (e.g. CD4+ T lymphocytes).
  • FDCs provide both antigen and other signals that are central to the induction and maintenance of specific antibody responses.
  • FDCs can play roles in both health and disease (e.g. HIV/AIDS, prion diseases and follicular lymphomas).

Keywords: follicular dendritic cells; secondary lymphoid tissues; germinal centres; anamnestic antibody responses; complement proteins and receptors; Fc receptors; antigen presentation to B‐lymphocytes; HIV reservoir; prions; follicular lymphoma and sarcoma

Figure 1. Light and electron micrographs of isolated FDCs. (a) Light micrograph of an FDC in suspension. Note the long dendritic processes emanating from the cell body. These processes allow intimate interactions with surrounding lymphocytes. The arrows indicate an FDC. (b) Scanning electron micrograph of an isolated FDC cultured on collagen type 1 illustrating the extensive dendritic networks generated in vitro. Reproduced from Dr. Andras K Szaka http://commons.wikimedia.org/wiki/File:Follicular_dendritic_cell.jpg Creative Commons Compatible License.
Figure 2. FDCs trapping fluorescently labelled ICs in vivo and in vitro. (a) Photomicrograph of FDCs in vivo demonstrating trapping of ovalbumin ICs (ovalbumin + antiovalbumin). The ICs on FDCs are detected using goat antibody directed against the antiovalbumin present in the immune complexes (i.e. goat‐anti‐IgG (blue)). The arrows designate two FDC networks containing trapped fluorescent ICs. (b) FDC‐trapping of fluorescent antigen in vitro. Ovalbumin ICs were incubated with highly enriched FDCs in culture. Detection of the FDC‐trapped antigen is performed using goat antibody specific for the IgG in the ovalbumin–anti‐ovalbumin complexes (red) and the FDCs are labelled using FDC‐M1 (blue). (c) Higher magnification of an isolated FDC with ICs labelled as in panel b. Contributed by Dr. John G. Tew.
Figure 3. Important FDC‐membrane‐associated signalling molecules. In experimental animals with specific Abs, ICs form instantaneously upon Ag challenge and are trapped by FDC‐Fcγ RIIB and CR1/2. The engagement of FDC‐FcγRIIB with ICs provides signals to FDCs that result in the production of BAFF and IL‐6. These same ICs also activate complement and generate C3 and C4 fragments that are covalently bound to FDC‐ICs and can also be seen ‘decorating’ the FDC membranes. C3 fragments (CD21 ligand) engage FDC‐CR1/2, whereas C4BP binds C4b and localises on the FDC‐ICs. The periodically arranged FDC‐ICs engage BCRs, and extensive BCR cross‐linking delivers an Ag‐specific stimulatory signal. FDC‐CD21‐ligand binds B‐cell CD21, FDC‐C4BP ligates B‐cell CD40, FDC‐BAFF engages B‐cell BAFF‐R, and FDC IL‐6 binds B‐cell IL‐6R, delivering additional co‐stimulatory signals that promote B‐cell activation, proliferation and differentiation. Contributed by Dr. John G. Tew.
Figure 4. FDC contributions in health and disease. FDCs serve as a repository of retained antigens important in maintaining IgG and IgE memory responses. In addition, FDCs provide signs that promote the germinal centre (GC) reaction and license macrophages (MO) to destroy and remove apoptotic cells from the GC. In disease, FDCs also play important roles, serving as a reservoir of infectious HIV, and a source of PrPC, the normal form of the prion protein. Furthermore, these cells appear to play roles in some malignancies and in Castleman disease.
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Tew JG, Wu J, Fakher M, Szakal AK and Qin D (2001) Beyond the necessity of T cell help. Trends in Immunology 22: 361–367.

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Wang, Changna, Ollerton, Matthew T, and Burton, Gregory F(Feb 2016) Follicular Dendritic Cells (B Lymphocyte Stimulating). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001129.pub3]