Follicular Dendritic Cells (B Lymphocyte Stimulating)

Mohey Eldin M El Shikh, Virginia Commonwealth University, Richmond, Virginia, USA
Rania M El Sayed, Virginia Commonwealth University, Richmond, Virginia, USA
John G Tew, Virginia Commonwealth University, Richmond, Virginia, USA
Gregory F Burton, Brigham Young University, Provo, Utah, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0001129.pub2

Follicular dendritic cells (FDCs) are unique immune system cells that contribute to the maintenance of humoral (i.e. antibody) immune responses. These cells are located in the follicles of secondary lymphoid tissues (e.g. lymph nodes and spleen), where they trap and retain antigens in the form of highly immunogenic immune complexes (ICs). FDC-ICs are composed of antigen plus specific antibody and/or complement proteins. These trapped antigens, combined with other soluble and membrane-bound signals contributed by FDCs, are essential to the development and maintenance of the germinal centre reaction and IgG and IgE responses respectively. FDCs also appear to contribute to initial IgM responses. In addition to their positive effects on humoral immunity, FDCs may promote diseases including HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome), prion diseases and follicular lymphomas. A better understanding of FDCs should permit better regulation of antibody responses and may also allow the amelioration of some disease states.

Key Concepts

  • Antigens are trapped and retained for months on the surfaces of follicular dendritic cells (FDCs) in secondary lymphoid tissues (e.g. spleen and lymph nodes).
  • FDC-trapped antigens maintain memory IgG and IgE immune responses.
  • FDC-ICs are highly immunogenic and minute quantities are sufficient to generate significant antibody responses.
  • 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: antigen-trapping; germinal centres; B-lymphocyte; HIV/AIDS; prion diseases

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. This micrograph was contributed by Dr. Andras K Szakal, Richmond, VA. It can also be viewed at: http://commons.wikimedia.org/wiki/File:Follicular_dendritic_cell.jpg
Figure 2. : FDCs trapping fluorescently labelled ICs in vivo and in vitro. (a) Photomicrograph of FDCs in vivo demonstrating trapping of ovalbumin ICs (ovalbumin+anti-ovalbumin). The ICs on FDCs are detected using goat antibody directed against the anti-ovalbumin 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.
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-FcRIIB and CR1/2. The engagement of FDC-FcRIIB 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 localizes 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.
close
 Further Reading
    Aguzzi A, Sigurdson C and Heikenwaelder M (2008) Molecular mechanisms of prion pathogenesis. Annual Reviews of Pathology: Mechanisums of Disease 3: 11–40.
    Allen CD and Cyster JG (2008) Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Seminal Immunology 20: 14–25.
    Aydar Y, Balogh P, Tew JG and Szakal AK (2004) Follicular dendritic cells in aging, a “bottle-neck” in the humoral immune response. Ageing Research Reviews 3: 15–29.
    Burton GF, Keele BF, Estes JD, Thacker TC and Gartner S (2002) Follicular dendritic cell contributions to HIV pathogenesis. Seminars in Immunology 14: 275–284.
    ePath FDC Network Website at: http://home.comcast.net/~aszakal/
    Fu YX and Chaplin DD (1999) Development and maturation of secondary lymphoid tissues. Annual Review of Immunology 17: 399–433.
    Kosco-Vilbois MH (2003) Are follicular dendritic cells really good for nothing? Nature Review of Immunology 3: 764–769.
    Kuppers R (2004) Prognosis in follicular lymphomas – it's in the microenvironment. New England Journal of Medicine 351: 2152–2153.
    Petrasch S, Brittinger G, Wacker HH, Schmitz J and Kosco-Vilbois M (1994) Follicular dendritic cells in non-Hodgkin's lymphomas. Leukemia & Lymphoma 15: 33–43.
    Szakal AK, Kosco MH and Tew JG (1989) Microanatomy of lymphoid tissue during the induction and maintenance of humoral immune responses: structure function relationships. Annual Review of Immunology 7: 91–109.
    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.

Related Sub-Topics:

Cells of the Immune System | Antibodies
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Follicular Dendritic Cells (B Lymphocyte Stimulating)
 
How to Cite close
El Shikh, Mohey Eldin M, El Sayed, Rania M, Tew, John G, and Burton, Gregory F(Sep 2009) Follicular Dendritic Cells (B Lymphocyte Stimulating). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001129.pub2]