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 FcγRIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking FcγRIIb 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 FcγRIIb and were protected from apoptosis. Human plasmablasts expressed FcγRIIb and were killed by crosslinking, as were FcγRIIb-expressing myeloma cells. Our results suggest that FcγRIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.
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We thank H. Wiklund for myeloma cell lines; T. Tsubata and R.A. Floto for constructs; S. Koenig (Macrogenics) for antibodies; C. Watson for Bim-knockout mice; S. Bolland and J. Ravetch for Fcgr2b−/− mice; L. Willcocks, A. Rankin, W. Ouwehand and N. Watkins and the staff and donors of the National Blood Service Cambridge Apheresis Clinic for human primary lymphocyte preparation; and P. Lyons and A. Strasser for advice. FcγRIIb-deficient mice on the BALB/c and C57BL/6 backgrounds were provided by J.V. Ravetch and S. Bolland (Rockefeller University); FCS Press software was from R. Hicks (University of Cambridge); EJM and LP-1 cells were from H. Wiklund (Uppsala University); and the construct expressing human FcγRIIb was from R.A. Floto (University of Cambridge). Supported by the Wellcome Trust (067543AIA), Deutsche Forschungsgemeinschaft (MA 2273/2-4 and MA 2273/4-2 to R.A.M.) and the National Health and Medical Research Council of Australia (D.M.T., K.F. and K.E.L.).
The authors declare no competing financial interests.
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Xiang, Z., Cutler, A., Brownlie, R. et al. FcγRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol 8, 419–429 (2007). https://doi.org/10.1038/ni1440
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