CD38 induces apoptosis of a murine pro-B leukemic cell line by a tyrosine kinase-dependent but ADP-ribosyl cyclase- and NAD glycohydrolase-independent mechanism

Int Immunol. 2006 Jul;18(7):1029-42. doi: 10.1093/intimm/dxl037. Epub 2006 May 23.


Cross-linking of CD38 on hematopoietic cells induces activation, proliferation and differentiation of mature T and B cells and mediates apoptosis of myeloid and lymphoid progenitor cells. In addition to acting as a signaling receptor, CD38 is also an enzyme capable of producing several calcium-mobilizing metabolites, including cyclic adenosine diphosphate ribose (cADPR). It has been previously postulated that the calcium-mobilizing metabolites produced by CD38 may regulate its receptor-based activities. To test this hypothesis, we examined whether the enzyme activity of CD38 controls the apoptosis of an anti-CD38-stimulated leukemic B cell. We show that anti-CD38-induced apoptosis of Ba/F3 cells, a murine pro-B cell line, is not affected by blocking the calcium-mobilizing activity of cADPR or by inhibiting intracellular or extracellular calcium mobilization. In addition, we demonstrate that blocking CD38 enzyme activity with 2'-deoxy-2'-fluoro-nicotinamide arabinoside adenine dinucleotide has no effect on apoptosis and that Ba/F3 cells expressing catalytically inactive mutant forms of CD38 still undergo apoptosis upon CD38 cross-linking. Instead, we find that anti-CD38-induced apoptosis is dependent on tyrosine kinase and caspase activation, and that this process appears to be potentiated by the presence of membrane microdomains. Thus, the receptor-mediated functions of CD38 can be separated from its enzyme activity in a murine leukemic cell line, suggesting that CD38 plays multiple, but independent, biologic roles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / antagonists & inhibitors
  • ADP-ribosyl Cyclase / immunology*
  • ADP-ribosyl Cyclase / metabolism
  • ADP-ribosyl Cyclase 1 / antagonists & inhibitors
  • ADP-ribosyl Cyclase 1 / immunology*
  • ADP-ribosyl Cyclase 1 / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclic ADP-Ribose / immunology
  • Cyclic ADP-Ribose / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Immunologic Capping / drug effects
  • Immunologic Capping / immunology
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Membrane Microdomains / enzymology
  • Membrane Microdomains / immunology
  • Mice
  • NAD / analogs & derivatives
  • NAD / pharmacology


  • Enzyme Inhibitors
  • NAD
  • nicotinamide arabinoside adenine dinucleotide
  • Cyclic ADP-Ribose
  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Calcium