Mice Deficient for the Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase CD38 Exhibit Altered Humoral Immune Responses

Author:

Cockayne Debra A.1,Muchamuel Tony1,Grimaldi J. Christopher1,Muller-Steffner Hélène1,Randall Troy D.1,Lund Frances E.1,Murray Richard1,Schuber Francis1,Howard Maureen C.1

Affiliation:

1. From the Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA and the Laboratoire de Chimie Bioorganique, Faculté de Pharmacie, Université Louis Pasteur, Strasbourg-Illkirch, France.

Abstract

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

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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