title: CD83 Modulates B Cell Activation and Germinal Center Responses.
abstract: CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83(-/-) mice have a strong reduction of CD4(+) T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell-specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo.
authors.affiliation: Department of Immune Modulation, University Hospital Erlangen, 91052 Erlangen, Germany;
authors.forename: Lena
authors.identifier: 0000-0002-5030-1720
authors.initials: L
authors.lastname: Krzyzak
authors.affiliation: Department of Immune Modulation, University Hospital Erlangen, 91052 Erlangen, Germany;
authors.forename: Christine
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany;
authors.forename: Anne
authors.initials: A
authors.lastname: Urbat
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Hutzler
authors.affiliation: Department of Dermatology, University Hospital Erlangen, 91052 Erlangen, Germany;
authors.forename: Christian
authors.identifier: 0000-0002-6676-0497
authors.initials: C
authors.lastname: Ostalecki
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany; and.
authors.forename: Joachim
authors.initials: J
authors.lastname: Gläsner
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany; and.
authors.forename: Andreas
authors.identifier: 0000-0002-3154-0638
authors.initials: A
authors.lastname: Hiergeist
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany; and.
authors.forename: André
authors.initials: A
authors.lastname: Gessner
authors.affiliation: Division of Genetics, Nikolaus Fiebiger Center for Molecular Medicine, University of Erlangen, 91058 Erlangen, Germany.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
authors.affiliation: Department of Immune Modulation, University Hospital Erlangen, 91052 Erlangen, Germany; lars.nitschke@fau.de alexander.steinkasserer@uk-erlangen.de.
authors.forename: Alexander
authors.identifier: 0000-0001-7187-6729
authors.initials: A
authors.lastname: Steinkasserer
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; lars.nitschke@fau.de alexander.steinkasserer@uk-erlangen.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D025065:Borrelia burgdorferi / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C497965:Cd86 protein, mouse