ROLE OF THE HUMAN CD38 MOLECULE IN B-CELL ACTIVATION AND PROLIFERATION

Human CD38 is a surface molecule which has been attributed the functio n of a signaling channel leading to cellular activation and proliferat ion, an ectoenzyme with multiple function as well as an inducer of Ca2 + mobilization from cytoplasmic stores. The effect mediated by CD38 ha ve been studied in different cell populations: the results obtained in human B cells are apparently contradictory, with CD38 simultaneously leading to apoptosis in early B cells while increasing survival in cel ls derived from lymph node germinal center. Other effects recently rep orted concern a different potential in terms of signaling in early B c ells and derived cell lines or in more detailed disease models of huma n leukemia, namely B chronic lymphocytic leukemia cells. To complete t he picture of the effects mediated by CD38 in the B cell compartment, we have studied the signals elicited by ligation of the human molecule in mature B cells from circulating pool and also from spleen of norma l individuals. The information obtained completes the picture of CD38 and mature B cells, where we also studied the contribution of relevant cytokines involved in maintenance and differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6. Our results indicate t hat human CD38 plays a key role as a co-receptor in mature B cells fro m normal individuals.