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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 321-333 |
| Number of pages | 13 |
| Journal | Nature Immunology |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 15 2017 |
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ASJC Scopus subject areas
- Immunology
Cite this
The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR. / Nguyen, Trang T T; Kläsener, Kathrin; Zürn, Christa; Castillo, Patricia A.; Brust-Mascher, Ingrid; Imai, Denise; Bevins, Charles L; Reardon, Colin; Reth, Michael; Baumgarth, Nicole.
In: Nature Immunology, Vol. 18, No. 3, 15.02.2017, p. 321-333.Research output: Contribution to journal › Article
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TY - JOUR
T1 - The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR
AU - Nguyen, Trang T T
AU - Kläsener, Kathrin
AU - Zürn, Christa
AU - Castillo, Patricia A.
AU - Brust-Mascher, Ingrid
AU - Imai, Denise
AU - Bevins, Charles L
AU - Reardon, Colin
AU - Reth, Michael
AU - Baumgarth, Nicole
PY - 2017/2/15
Y1 - 2017/2/15
N2 - 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.
AB - 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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U2 - 10.1038/ni.3677
DO - 10.1038/ni.3677
M3 - Article
VL - 18
SP - 321
EP - 333
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 3
ER -