Several cells have been described in lymphoid tissue which have long dendritic processes and are morphologically distinguishable from lymphocytes and typical macrophages. One such dendritic-type cell resides in the B-cell copartment of lymph nodes and spleen and is especially prominent in lymphoid follicles. A newly proposed system of nomenclature for dendritic-type cells (D-cells), recommends the name """"""""follicular dendritic cell"""""""" and the abbreviation """"""""FDC"""""""" for this D-cell. (Tew, Thobecke, and Steinman, 1982). The cardinal feature of this cell, which distinguishes it from other leukocytes including other D-cells, is its ability to trap and retain immune complexes for extended periods of time (e.g. T 1/2 of HSA on mouse FDCs is approximately 2 months (Tew, and Mandel, 1979). Although this cell has been observed in sections of lymphoid tissues and its morphology described in a number of studies, its immune functions remain obscure. In part this may be attributable to the fact that this cell is very large, fragile and, in work up to the present application, has never been clearly identified in vitro. Nevertheless data from our laboratory support the concept that antigen persisting in association with FDCs functions in an antibody feedback system to maintain and regulate serum antibody levels in vivo. Data supporting this hypothesis were recently summarized in Immunological Reviews (Tew, Phipps, and Mandel, 1980). In addition, it has been proposed that FDCs play a major role in the induction of B-cell memory. Data supporting this hypothesis were also recently reviewed (Klaus, et al., 1980). Our long term research objective is to thoroughly test these hypotheses and establish whether antigen persisting on FDCs plays the proposed roles in the maintenance of specific antibody levels and B-cell memory. We have now established methods for releasing intact FDCs fdrom lymph nodes and methods for enriching and identifying FDCs in culture. We are now proposing to carry out a second generation of experiments using isolated FDCs in vitro as well as in vivo. In addition, we propose to characterize FDCs with respect to their cell surface markers, properties in cell culture, antigen trapping ability, etc. We also propose to determine if FDCs are of bone marrow origin, document stages of FDC in differentiation and determine their role in stimulation B-cells and in germinal center formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017142-06
Application #
3126990
Study Section
Immunobiology Study Section (IMB)
Project Start
1980-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
El Shikh, Mohey Eldin; Kmieciak, Maciej; Manjili, Masoud H et al. (2013) Multi-therapeutic potential of autoantibodies induced by immune complexes trapped on follicular dendritic cells. Hum Vaccin Immunother 9:2434-44
El Shikh, Mohey Eldin M; El Sayed, Rania M; Sukumar, Selvakumar et al. (2010) Activation of B cells by antigens on follicular dendritic cells. Trends Immunol 31:205-11
El Shikh, Mohey Eldin M; El Sayed, Rania M; Szakal, Andras K et al. (2009) T-independent antibody responses to T-dependent antigens: a novel follicular dendritic cell-dependent activity. J Immunol 182:3482-91
El Shikh, Mohey Eldin M; El Sayed, Rania M; Wu, Yongzhong et al. (2007) TLR4 on follicular dendritic cells: an activation pathway that promotes accessory activity. J Immunol 179:4444-50
El Shikh, M E; El Sayed, R M; Tew, J G et al. (2007) Follicular dendritic cells stimulated by collagen type I develop dendrites and networks in vitro. Cell Tissue Res 329:81-9
El Shikh, Mohey Eldin; El Sayed, Rania; Szakal, Andras K et al. (2006) Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development. Eur J Immunol 36:2715-24
Sukumar, Selvakumar; Conrad, Daniel H; Szakal, Andras K et al. (2006) Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and follicular dendritic cells. J Immunol 176:4811-7
Tanaka, S; Fakher, M; Barbour, S E et al. (2006) Influence of proinflammatory cytokines on Actinobacillus actinomycetemcomitans specific IgG responses. J Periodontal Res 41:1-9
Sukumar, Selvakumar; Szakal, Andras K; Tew, John G (2006) Isolation of functionally active murine follicular dendritic cells. J Immunol Methods 313:81-95
Aydar, Yuksel; Sukumar, Selvakumar; Szakal, Andras K et al. (2005) The influence of immune complex-bearing follicular dendritic cells on the IgM response, Ig class switching, and production of high affinity IgG. J Immunol 174:5358-66

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