CD83 influences cell-surface MHC class II expression on B cells and other antigen-presenting cells
1 Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
2 Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan
3 Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
4 Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
5 Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan
Correspondence to: T. F. Tedder; E-mail: thomas.tedder{at}duke.edu
CD83 is a member of the Ig superfamily expressed primarily by mature dendritic cells (DCs). In mice, CD83 expression by thymic stromal cells regulates CD4+ T cell development, with CD83–/– mice demonstrating dramatic reductions in both thymus and peripheral CD4+ T cells. In this study, CD83 expression was also found to affect MHC class II antigen expression within the thymus and periphery. CD83 deficiency reduced cell-surface class II antigen expression by 25–50% on splenic B cells and DCs, thymic epithelial cells and peritoneal macrophages. Reduced class II expression was a stable and intrinsic property that resulted from increased internalization of class II from the surface of CD83–/– B cells. Otherwise, class II antigen transcription, intracellular expression, heterodimer structure, antigen processing and antigen presentation were normal. Reduced class II antigen expression was not the primary cause of the CD83–/– phenotype since thymocyte and peripheral T cell development was normal in class II+/– mice. Comparable blocks in CD4+ thymocyte development were also observed in CD83–/– and CD83–/–class II+/– littermates. TCR and CD69 expression patterns in CD83–/– mice further suggested that double-positive thymocytes proceed through the class II-dependent stages of positive selection in the absence of CD83. These studies further emphasize a role for CD83 in lymphocyte development and immune regulation and reveal an unexpected role for CD83 expression in influencing cell-surface MHC class II turnover.
Keywords: CD83, MHC class II, turnover, cell surface expression, B cell
* These authors contributed equally to this study and share first authorship.
Transmitting editor: S. Koyasu
Received 6 March 2007, accepted 13 April 2007.
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