HUMAN CD38 - A VERSATILE LEUKOCYTE MOLECULE WITH EMERGING CLINICAL PROSPECTIVES

The human CD38 antigen is a non lineage-restricted type II transmembra ne glycoprotein involved in lymphocyte activation and heterotypic cell adhesion. Furthermore, CD38 is an ectoenzyme whose extracellular doma in bears distinctive bifunctional enzymatic activities which lead to t he synthesis and hydrolysis of cyclic-ADP ribose. The enzymatic activi ties are likely to be involved in the array of biological responses th at result from the triggering of CD38 on hematopoietic cells by agonis tic antibodies. These responses in human T, B and NK cells include a g rowth co-stimulus and physical association to molecules relevant in si gnal transduction. The role of this protein in different cellular comp artments is yet to be clarified. However, the existence of a soluble f orm of CD38 and the ability of the membrane bound molecule to internal ize following appropriate stimuli suggest that the hypotheses of both extra-cellular and intra-cellular roles are equally plausible. Other m olecules, that display a high degree of sequence similarity with CD38 have been identified in man and mouse. As these molecules exhibit almo st identical enzymatic activities, they may constitute a new family of proteins. The definition of the role of CD38 in anchored or soluble f orm and in selected pathological conditions (e.g. X-linked agammaglobu linemia, HIV-1 infection and myeloma) may provide important insights i nto the physiological functions of CD38.