CD83 Expression Is a Sensitive Marker of Activation Required for B Cell and CD4+ T Cell Longevity In Vivo

Abstract

CD83 is a surface marker that differentiates immature and mature human dendritic cell populations. Thymic epithelial cell expression of CD83 is also necessary for efficient CD4+ T cell development in mice. The altered phenotypes of peripheral B and CD4+ T cells, and the reduction of peripheral CD4+ T cells in CD83−/− mice, suggest additional functions for CD83. To assess this, a panel of mAbs was generated to characterize mouse CD83 expression by peripheral leukocytes. As in humans, activation of conventional and plasmacytoid murine dendritic cell subsets led to rapid up-regulation of CD83 surface expression in mice. In primary and secondary lymphoid compartments, a subset of B cells expressed low-level CD83, while CD83 was not detected on resting T cells. However, CD83 was prominently up-regulated on the majority of spleen B and T cells within hours of activation in vitro. In vivo, a low dose of hen egg lysozyme (1 μg) induced significant CD83 but not CD69 expression by Ag-specific B cells within 4 h of Ag challenge. Although B cell development appeared normal in CD83−/− mice, B and CD4+ T cell expression of CD83 was required for lymphocyte longevity in adoptive transfer experiments. Thus, the restricted expression pattern of CD83, its rapid induction following B cell and T cell activation, and its requirement for B cell and CD4+ T cell longevity demonstrate that CD83 is a functionally significant and sensitive marker of early lymphocyte activation in vivo.

The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populationsin vivo

“…Recent reports have demonstrated that CD83 not only colocalizes with MHCII molecules but also modifies their turnover rate in B cells, T cells, and DCs (10,35). In addition, CD83 is required for the viability of B and CD4 ϩ T cells (10,35). Thus, the high levels of CD83 promoter activity that we observed in both immature and mature B cells may not only prepare these cells for activation but also provide a survival signal.…”

“…Prazma et al (10) have reported the up-regulation of CD83 on CD4 ϩ and CD8 ϩ T cells. Their observation that CD83 upregulation does not occur until 4-6 h after activation can be easily explained by results showing that neither CD83 promoter activity nor preformed intracellular CD83 molecules are present in naïve T cells.…”

“…Thus, CD83 induction occurs early during an immune response but the protein appears to be confined intracellularly in a much wider spectrum of cells than previously appreciated, with major concentrations being found in B cells, DCs, and CD4 ϩ T cells. Recent reports have demonstrated that CD83 not only colocalizes with MHCII molecules but also modifies their turnover rate in B cells, T cells, and DCs (10,35). In addition, CD83 is required for the viability of B and CD4 ϩ T cells (10,35).…”

“…Among these molecules is CD83, first described by Zhou et al (4), CD83 is one of the most useful markers for identifying mature DCs capable of activating naïve T cells (5)(6)(7)(8). CD83 expression also occurs on certain T cell subsets (9,10), B cells (10)(11)(12), and murine thymic epithelial cells (13,14). Studies of CD83 transcription have shown that it is mediated by NF-B during the induction of adaptive responses (15,16).…”

Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

“…Artificial overexpression of CD83 in CD83 transgenic (CD83tg) mice interfered with the splenic maturation of transitional to follicular B cells and with the peripheral survival of mature naive B cells, whereas CD83 deficiency on the B cells conferred a mild selection advantage in the periphery (28). Naive wild-type B cells rapidly up-regulated CD83 upon activation by BCR or TLR engagement in vitro (6) and in vivo (8,9). The overexpression of CD83 in vivo strongly interfered with the humoral response to thymus-dependent (TD) and thymus-independent (TI) model Ag immunization and to infection.…”