title: Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo.
abstract: Maintenance of immunological tolerance is crucial to prevent development of autoimmune disease. The production of autoantibodies is a hallmark of many autoimmune diseases and studies in mouse model systems suggest that inhibitory signaling molecules may be important checkpoints of humoral tolerance. By generating humanized mice with normal and functionally impaired Fcγ receptor IIB (FcγRIIB) variants, we show that the inhibitory Fcγ-receptor is a checkpoint of humoral tolerance in the human immune system in vivo. Impaired human FcγRIIB function resulted in the generation of higher levels of serum immunoglobulins, the production of different autoantibody specificities, and a higher proportion of human plasmablasts and plasma cells in vivo. Our results suggest that the inhibitory FcγRIIB may be an important checkpoint of humoral tolerance in the human immune system.
authors: Department of Biology, Institute of Genetics,  University of Erlangen-Nürnberg, 91058 Erlangen,  Germany.
authors: Anne
authors: A
authors: Baerenwaldt
authors: Anja
authors: A
authors: Lux
authors: Heike
authors: H
authors: Danzer
authors: Bernd M
authors: BM
authors: Spriewald
authors: Evelyn
authors: E
authors: Ullrich
authors: Gordon
authors: G
authors: Heidkamp
authors: Diana
authors: D
authors: Dudziak
authors: Falk
authors: F
authors: Nimmerjahn
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000737:chemistry*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007107:Immune System; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D017452:Receptors, IgG