1. The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR.
- Author
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Nguyen, Trang TT, Kläsener, Kathrin, Zürn, Christa, Castillo, Patricia A, Brust-Mascher, Ingrid, Imai, Denise M, Bevins, Charles L, Reardon, Colin, Reth, Michael, and Baumgarth, Nicole
- Subjects
B-Lymphocytes ,Th1 Cells ,Th2 Cells ,Cells ,Cultured ,Animals ,Mice ,Inbred C57BL ,Mice ,Knockout ,Mice ,Immunoglobulin M ,Receptors ,Antigen ,B-Cell ,Receptors ,Fc ,Cytokines ,Signal Transduction ,Cell Differentiation ,Gene Expression Regulation ,Female ,Male ,Precursor Cells ,B-Lymphoid ,Cells ,Cultured ,Inbred C57BL ,Knockout ,Receptors ,Antigen ,B-Cell ,Fc ,Precursor Cells ,B-Lymphoid ,Immunology - Abstract
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.
- Published
- 2017