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FcγRIIb 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 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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Figure 1: Nonspecific immunization reduces antigen-specific bone marrow plasma cell numbers and serum IgG.
Figure 2: Plasma cells express FcγRIIb.
Figure 3: Plasma cells sustain transcription of Fcgr2b mRNA.
Figure 4: FcγRIIb and the persistence of splenic plasmablasts and long-lived bone marrow plasma cells.
Figure 5: FcγRIIb crosslinking induces apoptosis of in vitro generated plasmablasts.
Figure 6: FcγRIIb crosslinking induces apoptosis of ex vivo plasma cells.
Figure 7: FcγRIIb crosslinking and apoptosis in plasma cells from autoimmune-prone mice, human plasmablasts and myeloma cells.


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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.).

Author information




A.J.C. mainly contributed to Figures 1,2,3,4e in collaboration with E.U.W., K.F., R.A.M. and D.M.T; Z.X. mainly contributed to Figures 4f,5,6,7 with contributions from R.J.B., K.E.L. and E.S.; A.J.C. and R.J.B. generated the transgenic mice; K.G.C.S. conceived and directed the experiments; and Z.X. and K.G.C.S. wrote the paper with input from all authors.

Corresponding author

Correspondence to Kenneth G C Smith.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Plasma cell purification and FcγRIIb expression. (PDF 119 kb)

Supplementary Fig. 2

Adoptive transfer of splenocytes does not induce a primary response. (PDF 162 kb)

Supplementary Fig. 3

FcγRIIb does not affect Ig secretion by individual plasma cells. (PDF 270 kb)

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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).

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