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Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in Lyme arthritis.
Elife. 2020 Jul 02; 9E

Abstract

Pathogen specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkpoint. Genetic differences between inbred mouse models and the outbred human population and allelic receptor variants not present in mice, however, argue for caution when directly translating these findings to the human system. By studying Borrelia burgdorferi infection in humanized mice reconstituted with human hematopoietic stem cells from donors homozygous for a functional or non-functional FcgRIIb allele, we show that the human inhibitory FcgRIIb is a critical checkpoint balancing protective and autoreactive immune responses, linking infection with induction of autoimmunity in the human immune system.

Authors+Show Affiliations

Biology, Division of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.Biomedicine, University Hospital Basel, Basel, Switzerland.Biology, Division of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.Biology, Division of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.Dermatology, University Hospital Erlangen, Erlangen, Germany.Dermatology, University Hospital Erlangen, Erlangen, Germany.Medicine III, University Hospital Erlangen, Erlangen, Germany.Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.Departemtn of Biology, Division of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32613944

Citation

Danzer, Heike, et al. "Human Fcγ-receptor IIb Modulates Pathogen-specific Versus Self-reactive Antibody Responses in Lyme Arthritis." ELife, vol. 9, 2020.
Danzer H, Glaesner J, Baerenwaldt A, et al. Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in Lyme arthritis. Elife. 2020;9.
Danzer, H., Glaesner, J., Baerenwaldt, A., Reitinger, C., Lux, A., Heger, L., Dudziak, D., Harrer, T., Gessner, A., & Nimmerjahn, F. (2020). Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in Lyme arthritis. ELife, 9. https://doi.org/10.7554/eLife.55319
Danzer H, et al. Human Fcγ-receptor IIb Modulates Pathogen-specific Versus Self-reactive Antibody Responses in Lyme Arthritis. Elife. 2020 Jul 2;9 PubMed PMID: 32613944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in Lyme arthritis. AU - Danzer,Heike, AU - Glaesner,Joachim, AU - Baerenwaldt,Anne, AU - Reitinger,Carmen, AU - Lux,Anja, AU - Heger,Lukas, AU - Dudziak,Diane, AU - Harrer,Thomas, AU - Gessner,André, AU - Nimmerjahn,Falk, Y1 - 2020/07/02/ PY - 2020/01/20/received PY - 2020/07/02/accepted PY - 2020/7/3/entrez KW - immunology KW - inflammation KW - mouse JF - eLife JO - Elife VL - 9 N2 - Pathogen specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkpoint. Genetic differences between inbred mouse models and the outbred human population and allelic receptor variants not present in mice, however, argue for caution when directly translating these findings to the human system. By studying Borrelia burgdorferi infection in humanized mice reconstituted with human hematopoietic stem cells from donors homozygous for a functional or non-functional FcgRIIb allele, we show that the human inhibitory FcgRIIb is a critical checkpoint balancing protective and autoreactive immune responses, linking infection with induction of autoimmunity in the human immune system. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/32613944/Human_Fcγ-receptor_IIb_modulates_pathogen-specific_versus_self-reactive_antibody_responses_in_Lyme_arthritis L2 - https://doi.org/10.7554/eLife.55319 DB - PRIME DP - Unbound Medicine ER -
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