CD95 (Fas) expression is regulated by sequestration in the Golgi complex in B-cell lymphoma

The CD95 (Fas) molecule transmits apoptotic signals important in B-cell development and the genesis of B-cell lymphoma. We have investigated the surface and intracellular expression of CD95 in Burkitt's lymphoma (BL) cells, an important non-Hodgkin's lymphoma of B-cell origin. Group I BL cells did not express CD95 at the cell surface, but contained high levels of this receptor in the cytoplasm. In contrast, group III BL cells expressed CD95 intracellularly and at the cell surface. In group I and group III BL cells, cytoplasmic CD95 was localized to the Golgi complex, as assessed by confocal immunofluorescence microscopy and subcellular fractionation followed by immunoblotting. Trafficking through the Golgi complex is regulated by elements within the target protein and cellular sorting mechanisms. CD95 contains candidate signals for interaction with trafficking machinery. Group I BL cells can be induced to upregulate surface expression of CD95 following CD40 ligation and certain group I BL cell lines drift invitro to a group III phenotype, with consequent surface expression of CD95. Taken together, these observations show that CD95 can either be retained in the Golgi complex or exported to the cell surface, and suggest that membrane trafficking has an important and previously unrecognized role in regulating CD95 expression in B lymphocytes.