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The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR

Nature Immunology volume 18, pages 321333 (2017) | Download Citation


The FcμR receptor for the crystallizable fragment (Fc) of immunoglobulin M (IgM) can function as a cell-surface receptor for secreted IgM on a variety of cell types. We found here that FcμR was also expressed in the trans-Golgi network of developing B cells, where it constrained transport of the IgM-isotype BCR (IgM-BCR) but not of the IgD-isotype BCR (IgD-BCR). In the absence of FcμR, the surface expression of IgM-BCR was increased, which resulted in enhanced tonic BCR signaling. B-cell-specific deficiency in FcμR enhanced the spontaneous differentiation of B-1 cells, which resulted in increased serum concentrations of natural IgM and dysregulated homeostasis of B-2 cells; this caused the spontaneous formation of germinal centers, increased titers of serum autoantibodies and excessive accumulation of B cells. Thus, FcμR serves as a critical regulator of B cell biology by constraining the transport and cell-surface expression of IgM-BCR.

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We thank A. Spinner for help with flow cytometry; A. Treister for FlowJo software; R. Pohlmeyer for sharing flow cytometry data; J. Yang (University of Freiburg) for the GFP-IgD plasmid; M. Cavallari for help with image analysis; H. Kubagawa (Deutsches Rheuma Forschungszentrum) for BM from mice with global Fcmr deficiency; and the UC Davis Mouse Biology Program for generating Fcmrflx/flxCd19-Cre mice. Supported by the US National Institutes of Health (AI51354, AI85568 and U19AI109962 to N.B.), the UC Davis Graduate Group in Immunology, a Vietnamese Education Fellowship (T.T.T.N.), a UC Davis Chancellor's Fellowship (N.B.), the Excellence Initiative of the German Federal and State Governments (EXC 294), the European Research Council (322972) and the DFG (TRR130 and project 111026 of the German Cancer Aid to M.R.).

Author information


  1. Center for Comparative Medicine, University of California, Davis, Davis, California, USA.

    • Trang T T Nguyen
    •  & Nicole Baumgarth
  2. Graduate Group in Immunology, University of California, Davis, Davis, California, USA.

    • Trang T T Nguyen
    • , Patricia A Castillo
    • , Charles L Bevins
    •  & Nicole Baumgarth
  3. BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.

    • Kathrin Kläsener
    •  & Michael Reth
  4. Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, Freiburg, Germany.

    • Kathrin Kläsener
    •  & Michael Reth
  5. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

    • Kathrin Kläsener
    • , Christa Zürn
    •  & Michael Reth
  6. Department of Medical Microbiology & Immunology, University of California, Davis, California, USA.

    • Patricia A Castillo
    •  & Charles L Bevins
  7. Department of Anatomy, Physiology & Cell Biology, University of California, Davis, California, USA.

    • Ingrid Brust-Mascher
    •  & Colin Reardon
  8. Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.

    • Denise M Imai
    •  & Nicole Baumgarth
  9. Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

    • Nicole Baumgarth


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T.T.T.N. and N.B. designed experiments, analyzed data and wrote the manuscripts; K.K., C.L.B. and M.R. provided help with experimental design; T.T.T.N., K.K., C.Z. and P.A.C. performed experiments; I.B.-M. and C.R. helped with STED and confocal microscopy and image analysis; D.M.I. performed pathological evaluation of Fcmrflx/flxCd19-Cre mice; and all authors provided edits to the manuscript.

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The authors declare no competing financial interests.

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