MICE DEFICIENT FOR THE ECTO-NICOTINAMIDE ADENINE-DINUCLEOTIDE GLYCOHYDROLASE CD38 EXHIBIT ALTERED HUMORAL IMMUNE-RESPONSES

CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide ( NAD(+)) glycohydrolase that is expressed on multiple hematopoietic cel ls. The extracellular domain of CD38 can mediate the catalysis of NAD( +) to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing seco nd messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In a ddition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-ce ll antigen receptor. To investigate the in vivo physiological function (s) of this novel class of ectoenzyme we generated mice carrying a nul l mutation in the CD38 gene. CD38(-/-) mice showed a complete loss of tissue-associated NAD(+) glycohydrolase activity, showing that the cla ssical NAD(+) glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on com mitted progenitors, we show that CD38 is not required for hematopoiesi s or lymphopoiesis, However, CD38(-/-) mice did exhibit marked deficie ncies in antibody responses to T-cell-dependent protein antigens and a ugmented antibody responses to at least one T-cell-independent type 2 polysaccharide antigen. These data suggest that CD38 may play an impor tant role in vivo in regulating humoral immune responses. (C) 1998 by The American Society of Hematology.