FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation.
These studies investigate how interactions between the BCR and FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcgammaRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)-containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcgammaRIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappaB activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcgammaRIIB with BLyS-mediated B-cell survival.
Crowley
Jenni E
JE
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Stadanlick
Jason E
JE
Cambier
John C
JC
Cancro
Michael P
MP
D000818:Animals; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D051020:bcl-X Protein / Q000235:genetics
D053264:B-Cell Activating Factor; C494812:Bcl2l1 protein, mouse; C499172:Fcgr2b protein, mouse; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008024:Ligands; D017452:Receptors, IgG; D051020:bcl-X Protein; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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