Ligation of CD38 suppresses human B lymphopoiesis.

摘要: CD38 is a transmembrane glycoprotein expressed in many cell types, including lymphoid progenitors and activated lymphocytes. High levels of expression on immature cells suggest its role the regulation growth differentiation, but there no evidence demonstrating functional activity these cells. We used stroma-supported cultures B anti-CD38 monoclonal antibodies (T16 IB4) to study function. In normal bone marrow CD19+ (n = 5), addition markedly reduced number recovered after 7 d. Cell loss was greatest among sIg- (mean recovery +/- SD 7.2 11.7% control cultures) extended CD19+CD34+ (the most subset; 7.6 2.2%). contrast, ligation did not substantially affect numbers peripheral blood or tonsillar 22 B-lineage acute lymphoblastic leukemia cases, suppressed leukemic also lines cultured stroma and, some presence stroma-derived cytokines (interleukin [IL] 7, IL-3, and/or stem factor), inhibit stroma- cytokine-free cultures. DNA content fragmentation studies showed that resulted both inhibition synthesis induction apoptosis. It known catalyzes nicotinamide adenine dinucleotide (NAD+) hydrolysis into cyclic ADP-ribose (cADPR) ADPR. However, changes NAD+ cADPR ADPR production were found by high-performance liquid chromatography; NAD+, ADPR, offset inhibitory effects anti-CD38. Thus, does suppress lymphopoiesis altering enzymatic function molecule. conclusion, data show inhibits microenvironment, interaction with putative ligand represents novel regulatory mechanism lymphopoiesis.