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The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR
Trang T T Nguyen1,2, Kathrin Kläsener3,4,5, Christa Zürn5
1Center for Comparative Medicine, University of California, Davis, Davis, California, USA.
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.
Insights
The Fc receptor for IgM (FcμR) regulates B cell development by controlling the surface expression of the IgM B cell receptor (IgM-BCR). Loss of FcμR leads to increased IgM-BCR signaling and autoimmune B cell responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The Fc receptor for the crystallizable fragment (Fc) of immunoglobulin M (IgM), known as FcμR, acts as a cell-surface receptor for secreted IgM.
- FcμR is expressed on various cell types and plays a role in immune responses.
Purpose of the Study:
- To investigate the role of FcμR in the trans-Golgi network of developing B cells.
- To determine how FcμR constrains the transport and cell-surface expression of the IgM-isotype B cell receptor (IgM-BCR).
Main Methods:
- Immunohistochemistry to detect FcμR localization in the trans-Golgi network.
- Analysis of B cell populations and serum immunoglobulin levels in FcμR-deficient mice.
- Flow cytometry to assess B cell receptor surface expression and signaling.
Main Results:
- FcμR is present in the trans-Golgi network of developing B cells, where it restricts IgM-BCR transport.
- Absence of FcμR leads to increased IgM-BCR surface expression and enhanced tonic BCR signaling.
- FcμR deficiency promotes spontaneous B-1 cell differentiation, increases natural IgM, dysregulates B-2 cell homeostasis, and causes autoimmune B cell responses.
Conclusions:
- FcμR is a critical regulator of B cell biology.
- FcμR constrains IgM-BCR transport and cell-surface expression, thereby controlling B cell signaling and homeostasis.
- Dysregulation of FcμR function contributes to autoimmune B cell activation and autoantibody production.
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