Autonomous SHIP-dependent FcgammaR signaling in pre-B cells leads to inhibition of cell migration and induction of cell death.
Mature B cells express a single immunoglobulin Fc receptor, FcgammaRIIB, that functions to block downstream signaling by co-aggregated antigen receptors. Co-aggregation of receptors is essential because BCR activated kinases must phosphorylate FcgammaRIIB to recruit SHIP and mediate inhibitory signals. Pre-B cells also express FcgammaRIIB, but since they do not yet express antigen receptor, it is unclear when they are activated physiologically. Here, we demonstrate that aggregation of the FcR on pre-B cells leads to potent inhibitory signaling. Aggregation of the FcR alone leads to downstream effects including the induction of cell death and the blockade of SDF-1 induced migration. The biochemical circuitry that mediates this response is unique because although SHIP is required for this signaling and is phosphorylated upon receptor aggregation, this occurs in the absence of FcgammaRIIB phosphorylation. Results indicate that immune complexes may inhibit B cell production in the bone marrow by antigen non-specific mechanisms.
Brauweiler
Anne M
AM
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Cambier
John C
JC
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017209:Apoptosis / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement / Q000276:immunology* / Q000502:physiology; D007138:Immunoglobulin delta-Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology* / Q000502:physiology; D010766:Phosphorylation; D017452:Receptors, IgG / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology* / Q000502:physiology
D015703:Antigens, CD; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D008565:Membrane Proteins; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases; D017452:Receptors, IgG; C080571:Fc gamma receptor IIB; C422105:SDF2L1 protein, human; C098706:INPPL1 protein, human