CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells.
The present study demonstrates that an agonistic anti-CD38 monoclonal antibody (mAb) (IB4) is capable of preventing apoptosis of human tonsillar germinal center (GC) B cells as measured by either morphological methods on Giemsa-stained cytospin preparations or flow cytometry on propidium iodide-stained cells. Two other anti-CD38 mAb (Leu-17 and OKT10) consistently failed to prevent apoptosis in the same cells, even when tested over a wide range of concentrations. Furthermore, exposure of GC B cells to IB4 mAb up-regulates the bcl-2 proto-oncogene product in a manner similar to that observed with CD40 ligand (CD40L). The ability of IB4 mAb to prevent apoptosis of GC B cells was inferior to that of both anti-CD40 mAb and CD40L. No synergistic or additive effects were observed when IB4 mAb was used together with CD40L. Unlike anti-CD40 mAb or CD40L, IB4 mAb neither induced a proliferation of GC B cells nor increased their proliferative response to anti-CD40, CD40L or recombinant interleukin-4, used alone or in combination. The present results are consistent with the recent findings on either the feature of the CD38 molecules to deliver activation signals and on the mechanisms of selection of B cells that operates in the GC.
Zupo
S
S
Laboratory of Clinical Immunology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Rugari
E
E
Dono
M
M
Taborelli
G
G
Malavasi
F
F
Ferrarini
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D014066:Palatine Tonsil / Q000166:cytology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1