Independently ligating CD38 and Fc gammaRIIB relays a dominant negative signal to B cells.

Academic Article

Abstract

  • CD38 is expressed on a variety of hematopoietic cells and has a unique enzymatic activity that converts nicotinamide adenine dinucleotide (NAD) into cyclic ADP-ribose (cADPR) and then into ADPR. CD38 is expressed at increasingly higher levels on B cells at each stage of B cell differentiation, and is then down-regulated on germinal center B cells and mature plasma cells. Crosslinking of CD38 on the surface of mature, resting B cells induces B-cell proliferation, which is enhanced by co-signals such as IL-4 and LPS. CD38-induced proliferation is abrogated by Fc gammaRIIB ligation and this inhibition can be effected by the addition of anti-Fc gammaRII Ab midway through a 48 h in vitro culture indicating that it delivers a potent negative signal to CD38 activated B cells. The suppressive signal was shown to occur through the Fc gammaRIIB because CD38-induced B-cell activation was not inhibited by the ligation of Fc gammaRIIB in Fc gammaRII-deficient B cells. These results indicate that Fc gammaRIIB can act as a regulatory molecule that modulates CD38 signals in vivo.
  • Published In

  • Hybridoma  Journal
  • Keywords

  • ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, Animals, Antibody Specificity, Antigens, CD, Antigens, Differentiation, B-Lymphocytes, Immunologic Capping, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, NAD+ Nucleosidase, Receptors, IgG, Signal Transduction
  • Digital Object Identifier (doi)

    Author List

  • Oliver AM; Grimaldi JC; Howard MC; Kearney JF
  • Start Page

  • 113
  • End Page

  • 119
  • Volume

  • 18
  • Issue

  • 2