Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss

Journal article


Publication Details

Author(s): Grötsch B, Lux A, Rombouts Y, Hoffmann A, Andreev D, Nimmerjahn F, Xiang W, Scherer HU, Schett G, Bozec A
Journal: Journal of Bone and Mineral Research
Publication year: 2019
ISSN: 0884-0431


Abstract

Next to proinflammatory cytokines, autoimmunity has been identified as a key trigger for osteoclast activation and bone loss. IgG-rheumatoid factor (IgG-RF) immune complexes, which are present in patients with rheumatoid arthritis, were shown to boost osteoclast differentiation. To date, the regulation of IgG-RF production in the absence of inflammatory triggers is unknown. Herein, we describe Fra1 as a key checkpoint that controls IgG-RF production by plasma cells and regulates autoimmune-mediated bone loss. Fra1 deficiency in B cells (Fra1ΔBcell ) led to increased IgG1-producing bone marrow plasma cells, enhanced IgG-RF production, and increased bone loss associated with elevated osteoclast numbers after immunization. The effect of IgG-RF on osteoclasts in vitro and on osteoclasts associated with bone loss in vivo was dependent on FcγR, especially FcγR3. Furthermore, immunization of WT mice with T-cell-dependent antigens induced a significant and robust decrease in Fra1 expression in bone marrow B cells, which was followed by increased IgG1 production and the induction of osteoclast-mediated bone loss. Overall, these data identify Fra1 as a key mediator of IgG-RF production and autoimmune-mediated bone loss. © 2019 American Society for Bone and Mineral Research.


FAU Authors / FAU Editors

Andreev, Darja
Medizinische Klinik 3 - Rheumatologie und Immunologie
Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Hoffmann, Alana
Professur für Molekulare Neurologie
Lux, Anja Dr.
Lehrstuhl für Genetik
Nimmerjahn, Falk Prof. Dr.
Lehrstuhl für Genetik
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Xiang, Wei PD Dr.
Lehrstuhl für Biochemie und Molekulare Medizin


External institutions with authors

Leiden University Medical Center


How to cite

APA:
Grötsch, B., Lux, A., Rombouts, Y., Hoffmann, A., Andreev, D., Nimmerjahn, F.,... Bozec, A. (2019). Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss. Journal of Bone and Mineral Research. https://dx.doi.org/10.1002/jbmr.3705

MLA:
Grötsch, Bettina, et al. "Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss." Journal of Bone and Mineral Research (2019).

BibTeX: 

Last updated on 2019-25-04 at 08:23