The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB.
Many studies have shown that FcgammaRIIB is a negative regulator of B cell receptor signaling, and even though FcgammaRIIB is expressed through all developmental stages of the B cell lineage, its involvement in pre-B cell receptor (pre-BCR) signaling has not been examined. To investigate FcgammaRIIB function at the pre-B cell stage, we have established pre-BCR positive pre-B cell lines from normal mice and FcgammaRIIB-deficient mice, named PreBR and Fcgamma(-/-)PreBR, respectively. These cell lines are able to differentiate into immature B cells in vitro by removal of IL-7. In PreBR, apoptosis was moderately induced by F(ab')(2) anti-mu Ab, but not by intact anti-mu Ab. Phosphorylation of SH2-containing inositol 5-phosphatase (SHIP) and Dok, which are involved in FcgammaRIIB signaling, was induced by anti-mu cross-linking in PreBR. In contrast, apoptosis was strongly induced by both the F(ab')(2) and intact anti-mu Abs in Fcgamma(-/-)PreBR, and the level of phosphorylation of SHIP or Dok was much lower in Fcgamma(-/-)PreBR than those observed in PreBR. Restoration of FcgammaRIIB to Fcgamma(-/-)PreBR followed by anti-mu cross-linking blocked severe apoptosis, and up-regulated SHIP and Dok phosphorylation. The results demonstrate that FcgammaRIIB negatively regulates pre-BCR-mediated signaling for apoptosis.
Kato
Ibuki
I
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
Takai
Toshiyuki
T
Kudo
Akira
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG