FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human
FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human
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DOI：
10.1038/s41467-019-09434-0
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发表时间：
2019-04-29
影响因子：
16.6
通讯作者：
Smith, Kenneth G. C.
中科院分区：
文献类型：
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作者：
Espeli, Marion;Bashford-Rogers, Rachael;Smith, Kenneth G. C.
B 细胞发育过程中存在多个耐受检查点，以控制自身反应性 B 细胞并防止致病性自身抗体的产生。 Fc gamma RIIb 是一种 Fc 受体，可抑制 B 细胞激活，如果存在缺陷，则与自身免疫性疾病相关，但其对特定 B 细胞耐受检查点的影响尚不清楚。在这里，我们发现 Fc γ RIIb 表达减少会增强自身反应性未成熟 B 细胞的缺失和无反应性，但相反会促进生发中心的自身反应性 B 细胞扩增和血清自身抗体的产生，甚至对外源性非自身抗原作出反应。因此，我们的数据表明 Fc γ RIIb 对免疫前和免疫后耐受检查点具有相反的作用，并表明 B 细胞耐受需要控制对免疫抗原具有低亲和力或无亲和力的旁观者生发中心 B 细胞。
Several tolerance checkpoints exist throughout B cell development to control autoreactive B cells and prevent the generation of pathogenic autoantibodies. Fc gamma RIIb is an Fc receptor that inhibits B cell activation and, if defective, is associated with autoimmune disease, yet its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of Fc gamma RIIb enhances the deletion and anergy of autoreactive immature B cells, but in contrast promotes autoreactive B cell expansion in the germinal center and serum autoantibody production, even in response to exogenous, non-self antigens. Our data thus show that Fc gamma RIIb has opposing effects on pre-immune and post-immune tolerance checkpoints, and suggest that B cell tolerance requires the control of bystander germinal center B cells with low or no affinity for the immunizing antigen.