POLYMERASE CHAIN-REACTION SELECTS A NOVEL DISINTEGRIN PROTEINASE FROMCD40-ACTIVATED GERMINAL CENTER DENDRITIC CELLS

To identify genes expressed by a specific subset of dendritic cells fo und in vivo a polymerase chain reaction-based cDNA subtraction techniq ue was applied to the recently described germinal center dendritic cel ls. A novel member of the disintegrin metalloproteinase family was clo ned which comprises a not typical zinc-chelating catalytic site most s imilar to a bacterial metalloproteinase. Dendritic cell precursors or immature dendritic cells express no or low levels of the message. It i s induced to high levels upon spontaneous or CD40-dependent maturation and in a mixed lymphocyte reaction. In situ hybridization showed dist inct expression of this gene in the germinal center. This, together wi th the findings that certain disintegrin metalloproteinases regulate t he activity of tumor necrosis factor alpha and that metalloproteinases have also been implicated in FasL processing, suggest that this novel molecule may play an important role in dendritic cell function and th eir interactions with germinal center T cells.