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

Trang T T Nguyen, Kathrin Kläsener, Christa Zürn, Patricia A. Castillo, Ingrid Brust-Mascher, Denise Imai, Charles L Bevins, Colin Reardon, Michael Reth, Nicole Baumgarth

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)321-333
Number of pages13
JournalNature Immunology
Volume18
Issue number3
DOIs
StatePublished - Feb 15 2017

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Immunoglobulin M
B-Lymphocytes
B-Cell Antigen Receptors
Immunoglobulin Fc Fragments
trans-Golgi Network
Immunoglobulin D
Germinal Center
Immunoglobulin Isotypes
Cell Surface Receptors
Serum
Autoantibodies
Cell Biology
immunoglobulin M receptor
Homeostasis

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 journalArticle

Nguyen TTT, Kläsener K, Zürn C, Castillo PA, Brust-Mascher I, Imai D et al. The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR. Nature Immunology. 2017 Feb 15;18(3):321-333. https://doi.org/10.1038/ni.3677
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. / The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR. In: Nature Immunology. 2017 ; Vol. 18, No. 3. pp. 321-333.
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