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Characterization of Human Monocyte-derived Dendritic Cells by Imaging Flow Cytometry: A Comparison between Two Monocyte Isolation Protocols
Published on: October 18, 2016
Follicular dendritic cells inhibit human B-lymphocyte proliferation
A S Freedman1, J M Munro, K Rhynhart
1Department of Medicine, Harvard Medical School, Boston, MA.
Insights
Follicular dendritic cells (FDCs) can inhibit B-cell proliferation. Metabolically active FDCs, but not fixed ones, suppress B-cell growth, suggesting a regulatory role in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- B lymphocytes interact with follicular dendritic cells (FDCs) in germinal centers.
- FDCs are hypothesized to regulate B-cell growth and differentiation via cell-cell interactions.
Purpose of the Study:
- To investigate the role of FDCs in regulating B-cell proliferation.
- To determine if FDCs can inhibit B-cell growth and differentiation.
Main Methods:
- Isolation of highly enriched FDCs using the monoclonal antibody DRC-1.
- Culture of irradiated FDCs with mitogen-stimulated B cells.
- Assessment of B-cell proliferation via 3H-TdR uptake.
- Analysis of the effect of FDC supernatants on B-cell proliferation.
Main Results:
- Irradiated FDCs inhibited B-cell proliferation by up to 80%.
- Paraformaldehyde-fixed FDCs did not inhibit B-cell proliferation, indicating the need for metabolic activity.
- Supernatants from cultured FDCs also demonstrated inhibitory effects on B-cell proliferation.
Conclusions:
- FDCs possess the ability to downregulate the clonal expansion of B cells.
- This inhibitory function of FDCs is crucial for normal immune responses within lymphoid follicles.
- Dysfunctional FDC inhibition may contribute to infectious and neoplastic diseases affecting germinal centers.
Abstract:
In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.
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