Identification and characterization of nuclear CD38 in the rat spleen

CD38 is an ectoenzyme, which can produce metabolites with intracellular Ca(2+) mobilizing properties and has multiple immunological functions. However, we have recently shown that CD38 is also localized to the nucleus of rat hepatocyte whereby its metabolite cADPR, is able to mobilize nuclear Ca(2+) stores. In this study, we further characterize the localization of nuclear CD38 in the spleen, an important immune organ. We managed to detect the presence of ADP-ribosyl cyclase activity in the nuclear fraction. With Western blotting, we managed to characterize a 42-45 kDa protein band that is typical of CD38 under reducing and non-reducing conditions. However, as a comparison, other nuclear fractions from tissues like thymus, cardiac muscle and cerebellum yielded an additional 85 kDa protein band under non-reducing conditions. Both protein bands could be blocked with a CD38 blocking peptide. Immunohistochemical studies revealed the expression of CD38 in the marginal zone and in the red pulp. In contrast, the germinal center remained largely immunonegative for CD38. This is the first report of a functionally active ADP-ribosyl cyclase/CD38 in the spleen nuclear fraction. The results here suggest that the presence of CD38 in the nuclear environment might have a corollary to functional and regulatory roles in the nucleus.