期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 46, 页码 18772-18777出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1111810108
关键词
Fc-receptor; systemic lupus erythematosus
资金
- Bavarian Genome Research Network
- German Research Foundation [FOR 832]
- Emmy-Noether Programme
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 Fc gamma receptor IIB (Fc gamma RIIB) variants, we show that the inhibitory Fc gamma-receptor is a checkpoint of humoral tolerance in the human immune system in vivo. Impaired human Fc gamma RIIB 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 Fc gamma RIIB may be an important checkpoint of humoral tolerance in the human immune system.
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