Human keratinocytes regulate their expression of B7/BB-1 antigen by a unique, calcium-dependent mechanism

Previous studies of normal human keratinocytes have indicated that these cells express BB-1 antigen, an important adherence molecule usually associated with "professional" antigen-presenting cells. We studied freshly isolated epidermal cells and noted that the frequency of BB-1-positive cells in normal human skin varied from 2.6 to 7.4% of total epidermal cells. Two-color flow cytometry confirmed that keratinocytes were the major cell in the epidermis that expressed BB-1, because less than 10% of total epidermal Langerhans cells were positive for BB-1. Northern blot analysis of RNA extracted from normal human epidermis revealed low levels of 1.7-kb B7-1 transcripts, which were independent of the presence of epidermal Langerhans cells, again indicating that such transcripts were derived from keratinocytes. Keratinocytes cultured in medium containing low concentrations of extracellular calcium (0.07 mM) expressed low levels of cell-surface BB-1. However, keratinocytes cultured in medium with higher levels of extracellular calcium (1.5 mM) lost cell-surface expression of BB-1. Similarly, low-calcium keratinocytes expressed the 1.7- and 2.9-kb B7-1 transcripts, whereas high-calcium keratinocytes expressed only the 1.7-kb transcript. Studies of the cell-surface expression of BB-1 by plastic adherent monocytes indicated that such cells do not respond to similar changes in extracellular calcium concentrations. Calcium-induced differentiation of keratinocytes regulates the expression of BB-1 antigen as well as transcripts, which is a novel mechanism for the regulation of this molecule.