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Published on: July 9, 2008
Activation of B lymphocyte maturation by a human follicular dendritic cell line, FDC-1
E A Clark1, K H Grabstein, A M Gown
1Department of Microbiology, University of Washington Medical Center, Seattle 98195, USA.
Insights
Follicular dendritic cell line FDC-1 stimulates B cell antibody production, including IgM and IgG, through both cell contact and soluble factors. This suggests a role for FDC-1 in B cell immunity and potential links to stromal cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Follicular dendritic cells (FDCs) are crucial for B cell maturation and antibody production.
- A previously described cell line, FDC-1, derived from human tonsillar cells, exhibits characteristics related to FDCs.
Purpose of the Study:
- To investigate the capacity of the FDC-1 cell line to induce B cell antibody production.
- To elucidate the mechanisms, including cell contact and soluble factors, involved in FDC-1 mediated B cell stimulation.
- To compare the immunophenotype of FDC-1 cells with other cell types like human foreskin fibroblasts (HFF).
Main Methods:
- Culturing B cells with FDC-1 cells and analyzing immunoglobulin (IgM, IgG) production.
- Assessing the role of cell contact by using fixed FDC-1 cells and cell-free supernatants.
- Investigating the effects of cytokines (IL-6, IL-7, IL-4) on FDC-dependent Ig production.
- Comparing FDC-1 cells with epithelial cell lines and HFF using immunophenotyping (CD40, CD54, CD73, CD74, NGFR, smooth muscle actin, BST-1).
Main Results:
- FDC-1 cells significantly augmented B cell production of IgM and IgG.
- As few as 50-100 FDC-1 cells increased B cell IgM production 10- to 100-fold.
- Both cell contact and soluble factors from FDC-1 cells contributed to Ig production.
- Supernatants from FDC-1 cells stimulated IgM production, indicating soluble B cell stimulating factors.
- FDC-1 cells expressed specific markers (CD40, CD54, CD73, CD74, NGFR, smooth muscle actin, BST-1) differentiating them from HFF and suggesting a stromal cell lineage.
Conclusions:
- The FDC-1 cell line effectively stimulates B cell antibody production, mimicking some functions of primary FDCs.
- Both direct cell contact and soluble mediators released by FDC-1 cells are involved in B cell activation.
- The unique marker expression profile of FDC-1 cells suggests a potential relationship with fibroblast/stromal cell lineages.
Abstract:
Previously, we described the characteristics of a cell line that is derived from a low density fraction of human tonsillar cells and, on the basis of a number of criteria, is related to follicular dendritic cells (FDC). This line, FDC-1, binds B lymphocytes and not T lymphocytes, and promotes anti-Ig- or anti-CD40-induced B cell proliferation. In this work, we show that culturing B cells with small numbers of FDC-1 cells leads to significant production of IL-6 and of both IgM and IgG. As few as 50 to 100 FDC-1 augmented B cell IgM production by 10- to 100-fold. Although fixed FDC-1 cells, unlike live FDC-1 cells, do not stimulate Ig production, cell contact is not required for all FDC-dependent Ig production. Supernatants from cultured FDC-1 cells can also stimulate B cells to produce IgM, suggesting that FDC produce a soluble B cell stimulating factor(s). Augmentation of FDC-dependent IgM production by either IL-6 or IL-7 and augmentation of FDC-dependent IgG production by IL-4 does require FDC-1 cells to be in contact with B cells. When the effects of FDC-1 cells were compared with those of epithelial cell lines and human foreskin fibroblasts (HFF), both FDC-1 cells and HFF induced B cells to produce IgM. FDC-1, unlike HFF, were positive for CD40, CD54, CD73, CD74, and nerve growth factor receptor (NGFR), and unlike HFF, but like certain stromal cells, FDC-1 cells also expressed smooth muscle actin, and a novel marker for stromal cells, BST-1. The possible relationship of FDC-1 cells and FDC in general to a fibroblast/stromal cell lineage is discussed.
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