THE LYMPHOCYTE SURFACE-ANTIGEN CD38 ACTS AS A NICOTINAMIDE ADENINE-DINUCLEOTIDE GLYCOHYDROLASE IN HUMAN T-LYMPHOCYTES

The extracellular domain of the lymphocyte surface antigen CD38 has been recently shown to share a high sequence homology with a nicotinamide adenine dinucleotide (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod Aplysia (E. States, D. J., Walseth, T. E, Lee, H. C., Trends Biochem. Sci. 1992. 17: 495). In agreement with this finding, we present here evidence that CD38-overexpressing T cells, such as human thymocytes and cells from the human HPB-ALL T cell line, exhibit a NAD+-hydrolyzing enzymatic activity present on the outer surface of the cell membrane. In contrast, T lymphocytes with relatively low levels of CD38 marker, such as the human Jurkat cell line, display a lower activity. This suggests a relationship between ecto-NAD+ glycohydrolase activity and CD38 expression, as confirmed here when comparing wild-type Jurkat cells and a Jurkat cell variant overexpressing the CD38 molecule. Moreover, CD38 immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase enzyme: it transforms NAD+ stoichiometrically into nicotinamide plus adenosine 5'-diphosphoribose. Altogether these results strongly support the assumption that CD38 is actually a lymphocyte-specific NAD+-hydrolyzing enzyme, a finding that give new prospects to understand the in vivo function of this cell membrane protein.