title: Molecular requirements of the B-cell antigen receptor for sensing monovalent antigens.
abstract: How the B-cell antigen receptor (BCR) is activated upon interaction with its cognate antigen or with anti-BCR antibodies is not fully understood. We have recently shown that B-cell activation is accompanied by the opening of the pre-organized BCR oligomers, an observation that strengthens the role of receptor reorganization in signalling. We have now analysed the BCR oligomer opening and signalling upon treatment with different monovalent stimuli. Our results indicate that monovalent antigens are able to disturb and open the BCR oligomer, but that this requires the presence and activity of the Src family kinase (SFK) Lyn. We have also shown that monovalent Fab fragments of anti-BCR antibodies can open the BCR oligomers as long as they directly interact with the antigen-binding site. We found that monovalent antigen binding opens both the IgM-BCR and IgD-BCR, but calcium signalling is only seen in cells expressing IgM-BCR; this provides a molecular basis for IgM- and IgD-BCR functional segregation.
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Volkmann
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Naema
authors.initials: N
authors.lastname: Brings
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Becker
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.|Institute of Immunology University Hospital Ulm, Ulm, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Hobeika
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany yang@immunbio.mpg.de Michael.Reth@bioss.uni-freiburg.de.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.|Freiburg Institute for Advanced Studies (FRIAS) University of Freiburg, Freiburg, Germany.|University of Strasbourg Institute for Advanced Study (USIAS) University of Strasbourg, Strasbourg, France.
authors.forename: Jianying
authors.identifier: 0000-0001-8197-5413
authors.initials: J
authors.lastname: Yang
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany yang@immunbio.mpg.de Michael.Reth@bioss.uni-freiburg.de.|Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008822:Mice, Transgenic; D009592:Nitrohydroxyiodophenylacetate / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D009592:Nitrohydroxyiodophenylacetate; D012710:Serum Albumin, Bovine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: B‐cell antigen receptor; dissociation activation; monomeric antigen