CD83 influences cell-surface MHC class II expression on B cells and other antigen-presenting cells

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.