FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis.
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.
Xiang
Zou
Z
Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2OY, UK.
Cutler
Antony J
AJ
Brownlie
Rebecca J
RJ
Fairfax
Kirsten
K
Lawlor
Kate E
KE
Severinson
Eva
E
Walker
Elizabeth U
EU
Manz
Rudolf A
RA
Tarlinton
David M
DM
Smith
Kenneth G C
KG
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
C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012313:RNA