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A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal
B D Hock1, M Kato, J L McKenzie
1Haematology/Immunology Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand.
Insights
Researchers discovered a soluble form of CD83 (sCD83), which is released from membrane CD83 (mCD83) on activated immune cells. This finding may help uncover the function of CD83.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD83 is a glycoprotein primarily expressed on dendritic cells (DCs) and B lymphocytes.
- Membrane CD83 (mCD83) expression marks activated DCs, but its function and ligands remain unknown.
Purpose of the Study:
- To investigate the existence and origin of a soluble form of CD83 (sCD83).
- To explore the relationship between mCD83 expression and sCD83 release.
- To determine the presence of sCD83 in human circulation.
Main Methods:
- Utilized sCD83-specific ELISA and Western blotting to detect sCD83.
- Assessed sCD83 release from various cell lines and primary immune cells (B lymphocytes, monocyte-derived DCs).
- Investigated the effect of inhibiting protein synthesis on sCD83 release.
- Analyzed sCD83 levels in sera from healthy donors.
Main Results:
- Demonstrated the release of sCD83 from mCD83-expressing cell lines.
- Showed that sCD83 release is likely due to the shedding of mCD83, not de novo synthesis.
- Observed increased sCD83 release upon differentiation/activation of B lymphocytes and DCs.
- Detected low levels of circulating sCD83 in normal human sera.
Conclusions:
- Confirmed the existence of soluble CD83 (sCD83) released from membrane CD83 (mCD83).
- Suggests that sCD83 is shed from mCD83 on activated immune cells.
- The presence of sCD83 in circulation warrants further investigation into its biological role and potential ligands.
Abstract:
CD83 is an inducible glycoprotein expressed predominantly by dendritic cells (DC) and B lymphocytes. Expression of membrane CD83 (mCD83) is widely used as a marker of differentiated/activated DC but its function and ligand(s) are presently unknown. We report the existence of a soluble form of CD83 (sCD83). Using both a sCD83-specific ELISA and Western blotting, we could demonstrate the release of sCD83 by mCD83(+) B cell and Hodgkin's disease-derived cell lines, but not mCD83(-) cells. Inhibition of de novo protein synthesis did not affect the release of sCD83 during short-term (2 h) culture of cell lines although mCD83 expression was significantly reduced, suggesting sCD83 is generated by the release of mCD83. Isolated tonsillar B lymphocytes and monocyte-derived DC, which are mCD83(low), released only low levels of sCD83 during culture. However, the differentiation/activation of these populations both up-regulated mCD83 and increased sCD83 release significantly. Analysis of sera from normal donors demonstrated the presence of low levels (121 +/- 3.6 pg/ml) of circulating sCD83. Further studies utilizing purified sCD83 and the analysis of sCD83 levels in disease may provide clues to the function and ligand(s) of CD83.
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