title: The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR.
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.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, Davis, California, USA.|Graduate Group in Immunology, University of California, Davis, Davis, California, USA.
authors.forename: Trang T T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.|Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kläsener
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Zürn
authors.affiliation: Graduate Group in Immunology, University of California, Davis, Davis, California, USA.|Department of Medical Microbiology &Immunology, University of California, Davis, California, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Castillo
authors.affiliation: Department of Anatomy, Physiology &Cell Biology, University of California, Davis, California, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brust-Mascher
authors.affiliation: Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Imai
authors.affiliation: Graduate Group in Immunology, University of California, Davis, Davis, California, USA.|Department of Medical Microbiology &Immunology, University of California, Davis, California, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.affiliation: Department of Anatomy, Physiology &Cell Biology, University of California, Davis, California, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Reardon
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.|Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.affiliation: Center for Comparative Medicine, University of California, Davis, Davis, California, USA.|Graduate Group in Immunology, University of California, Davis, Davis, California, USA.|Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.|Department of Pathology, Microbiology &Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc