title: Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production.
abstract: Secondary antibody responses are marked by faster kinetics, improved antibody affinity and a switch from IgM to other immunoglobulin isotypes, most notably IgG, compared with primary responses. These changes protect from reinfection and represent the principle of most vaccination strategies. Yet, the molecular mechanisms that underlie B-cell memory responses are unclear. Here we show, by inactivating the immunoglobulin tail tyrosine (ITT) signalling motif of membrane-bound IgG1 in the mouse, that the ITT facilitates maintenance and reactivation of IgG-switched memory B cells in vivo. The ITT motif equips IgG-switched cells with enhanced BCR signalling capacity, which supports their competitiveness in secondary immune reactions and drives the formation of IgG-secreting plasma cells even in the absence of T-cell help. Our results demonstrate that ITT signalling promotes the vigorous production of IgG antibodies and thus provide a molecular basis for humoral immunological memory.
authors.affiliation: Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Medical Faculty, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lutz
authors.affiliation: Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Medical Faculty, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Dittmann
authors.affiliation: Max Planck Institute of Neurobiology, Transgenic Core Facility, 82152 Martinsried, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.affiliation: Hematopoiesis Unit, Department of Biology, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
authors.affiliation: Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Medical Faculty, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
authors.affiliation: Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Medical Faculty, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Engels
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D002118:Calcium
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