Abstract CD83 is predominantly known as a surface marker that defines mature DCs. The generation of CD83−/− mice further demonstrates that thymic epithelial expression of CD83 plays a significant role in the efficient generation of CD4 single positive thymocytes. The altered phenotype and reduced number of peripheral CD4+ T cells in CD83−/− mice further suggests a role for CD83 in the peripheral lymphocyte function. With regards to the surface expression pattern of CD83, CD83 was detected in the thymic medullary compartment and was specifically detected on thymic DCs and B cells in the mouse. Peripheral CD83 expression is limited to low level expression by resting follicular B cells but is quickly upregulated and transiently expressed on nearly 90% of spleen B220+ cells within 4 h of in vivo stimulation. Additionally, the majority (> 70%) of adoptively transferred B cells, expressing a BCR specific to hen egg lysozyme (HEL), expressed CD83 within 4 h of administration of a low dose of soluble HEL. At this timepoint, and low dose of antigen, less than 20% of B220+ splenocytes expressed CD69. Thus, the restricted expression pattern of CD83 and its near immediate upregulation on B cells in response to various stimuli suggest that CD83 is a sensitive, early activation marker of B cells.