title: A humanized mouse identifies the bone marrow as a niche with low therapeutic IgG activity.
abstract: Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG) activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal model system that allowed us to study human IgG effector functions in the context of an intact human immune system without the interference of murine Fcγ receptors expressed on mouse innate immune effector cells in vivo. Using a model of B cell depletion with different human IgG variants that recognize CD20, we show that this humanized mouse model can provide unique insights into the mechanism of human IgG activity in vivo. Importantly, these studies identify the bone marrow as a niche with low therapeutic IgG activity.
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lux
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Seeling
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Baerenwaldt
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lehmann
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany.
authors.forename: Inessa
authors.initials: I
authors.lastname: Schwab
authors.affiliation: Medical Department V, Klinikum am Bruderwald, Bugerstrasse 80, 96049 Bamberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Repp
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University Hospital of Erlangen, Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Meidenbauer
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University Hospital of Erlangen, Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
authors.affiliation: Department of Pathology, University Hospital of Erlangen, Krankenhausstrasse 8, 91054 Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Dermatology, University Hospital of Erlangen, Hartmannstrasse 14, 91052 Erlangen, Germany.
authors.forename: Gordon
authors.initials: G
authors.lastname: Heidkamp
authors.affiliation: Department of Dermatology, University Hospital of Erlangen, Hartmannstrasse 14, 91052 Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.affiliation: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058 Erlangen, Germany. Electronic address: falk.nimmerjahn@fau.de.
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG