Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo
Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo
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DOI：
10.1073/pnas.1111810108
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发表时间：
2011-11-15
影响因子：
11.1
通讯作者：
Nimmerjahn, Falk
中科院分区：
文献类型：
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作者：
Baerenwaldt, Anne;Lux, Anja;Nimmerjahn, Falk
维持免疫耐受对于预防自身免疫性疾病的发展至关重要。自身抗体的产生是许多自身免疫性疾病的标志，并且在小鼠模型系统中的研究表明，抑制性信号分子可能是体液耐受的重要检查点。通过产生具有正常和功能受损的Fc γ受体IIB（Fc γ RIIB）变体的人源化小鼠，我们表明抑制性Fc γ受体是体内人免疫系统中体液耐受的检查点。人Fc γ RIIB功能受损导致产生更高水平的血清免疫球蛋白，产生不同的自身抗体特异性，以及体内更高比例的人浆母细胞和浆细胞。我们的结果表明，抑制性Fc γ RIIB可能是人类免疫系统中体液耐受的重要检查点。
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.