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

Nat Immunol. 2017 Mar;18(3):321-333. doi: 10.1038/ni.3677. Epub 2017 Jan 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / physiology*
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Fc / metabolism*
  • Signal Transduction
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Cytokines
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell
  • Receptors, Fc