Independently ligating CD38 and Fc gammaRIIB relays a dominant negative signal to B cells.
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.
Oliver
A M
AM
Department of Microbiology, University of Alabama at Birmingham, 35294-3300, USA.
Grimaldi
J C
JC
Howard
M C
MC
Kearney
J F
JF
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D007152:Immunologic Capping; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009244:NAD+ Nucleosidase / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D015703:Antigens, CD; D000943:Antigens, Differentiation; C080571:Fc gamma receptor IIB; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1