title: FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis.
abstract: The survival of long-lived plasma cells, which produce most serum immunoglobulin, is central to humoral immunity. We found here that the inhibitory Fc receptor FcgammaRIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking FcgammaRIIb induced apoptosis of plasma cells, which we propose contributes to the control of their homeostasis and suggests a method for therapeutic deletion. Plasma cells from mice prone to systemic lupus erythematosus did not express FcgammaRIIb and were protected from apoptosis. Human plasmablasts expressed FcgammaRIIb and were killed by crosslinking, as were FcgammaRIIb-expressing myeloma cells. Our results suggest that FcgammaRIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.
authors.affiliation: Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2OY, UK.
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Brownlie
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fairfax
authors.forename: Kate E
authors.initials: KE
authors.lastname: Lawlor
authors.forename: Eva
authors.initials: E
authors.lastname: Severinson
authors.forename: Elizabeth U
authors.initials: EU
authors.lastname: Walker
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D016688:Mice, Inbred NOD; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012313:RNA