The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR
| Autor: | Charles L. Bevins, Trang T. T. Nguyen, Denise M Imai, Michael Reth, Christa Zürn, Colin Reardon, Patricia A. Castillo, Nicole Baumgarth, Kathrin Kläsener, Ingrid Brust-Mascher |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cell type Precursor Cells Cellular differentiation Cells Knockout B-cell receptor Immunology Inbred C57BL Autoimmune Disease Vaccine Related 03 medical and health sciences Mice Th2 Cells Biodefense hemic and lymphatic diseases Receptors Immunology and Allergy Animals Receptor B-Lymphoid B-Lymphocytes Cultured biology Fc Chemistry Prevention breakpoint cluster region B-Cell Germinal center Cell Differentiation Th1 Cells Cell biology 030104 developmental biology Immunoglobulin M Gene Expression Regulation Antigen biology.protein Cancer research Cytokines Female Signal transduction Signal Transduction |
| Zdroj: | Nature immunology, vol 18, iss 3 Nature Immunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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