title: Responsiveness of B cells is regulated by the hinge region of IgD.
abstract: Mature B cells express immunoglobulin M (IgM)- and IgD-isotype B cell antigen receptors, but the importance of IgD for B cell function has been unclear. By using a cellular in vitro system and corresponding mouse models, we found that antigens with low valence activated IgM receptors but failed to trigger IgD signaling, whereas polyvalent antigens activated both receptor types. Investigations of the molecular mechanism showed that deletion of the IgD-specific hinge region rendered IgD responsive to monovalent antigen, whereas transferring the hinge to IgM resulted in responsiveness only to polyvalent antigen. Our data suggest that the increased IgD/IgM ratio on conventional B-2 cells is important for preferential immune responses to antigens in immune complexes, and that the increased IgM expression on B-1 cells is essential for B-1 cell homeostasis and function.
authors.affiliation: Institute of Immunology, University Hospital Ulm, Ulm, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Übelhart
authors.affiliation: Institute of Immunology, University Hospital Ulm, Ulm, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hug
authors.affiliation: Institute of Immunology, University Hospital Ulm, Ulm, Germany.
authors.forename: Martina P
authors.initials: MP
authors.lastname: Bach
authors.affiliation: BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wossning
authors.affiliation: 1] Institute of Immunology, University Hospital Ulm, Ulm, Germany. [2] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dühren-von Minden
authors.affiliation: Department of Bioinformatics, Institute for Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Anselm H C
authors.initials: AH
authors.lastname: Horn
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine (CeMM), Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiantoulas
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kometani
authors.affiliation: 1] Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Turumi-ku, Kanagawa, Japan. [2] Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine (CeMM), Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.affiliation: Department of Bioinformatics, Institute for Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.affiliation: Chair of Genetics, Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.affiliation: 1] BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [2] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [3] Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.affiliation: 1] Institute of Immunology, University Hospital Ulm, Ulm, Germany. [2] BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [3] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
authors.forename: Hassan
authors.initials: H
authors.lastname: Jumaa
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D020013:Calcium Signaling / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D052058:Hinge Exons / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D056724:Immunity, Humoral / Q000235:genetics; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015202:Protein Engineering; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D000936:Antigen-Antibody Complex; D000941:Antigens; D007072:Immunoglobulin D; D007075:Immunoglobulin M
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