Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis
Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis
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DOI：
10.1016/s1074-7613(00)00027-3
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发表时间：
2000-08-01
期刊：
影响因子：
32.4
通讯作者：
Ravetch, JV
中科院分区：
文献类型：
--
作者：
Bolland, S;Ravetch, JV
凭借其将BCR偶联到抑制途径的能力，Fc-Gamma RIIB可能决定B细胞在免疫复合物结合时的命运。我们现在通过观察到RIIB-/-小鼠以一种依赖菌株的方式发展自身抗体和自身免疫性肾小球肾炎，为Fc-Gamma RIIB作为外周耐受途径的一个组成部分提供了证据。自身免疫表型的转移与供者RIIB-/-B细胞的存在有关，其中RIIB+/+髓系细胞主要来自受者。这些结果表明，B细胞上RIIB的缺失导致特定遗传背景下的自身免疫性疾病，从而确定其是上位性修饰物影响自身免疫发展的易感因素。
By virtue of its ability to couple the BCR to an inhibitory pathway, Fc gamma RIIB can potentially determine the fate of B cells upon IgG immune complex engagement. We now provide evidence for Fc gamma RIIB as a component of a peripheral tolerance pathway with the observation that RIIB-/- mice develop autoantibodies and autoimmune glomerulonephritis in a strain-dependent fashion. Transfer of the autoimmune phenotype is associated with the presence of donor RIIB-/- B cells, with the RIIB+/+ myeloid cells primarily derived from the recipient. These results suggest that deficiency of RIIB on B cells leads to autoimmune disease in specific genetic backgrounds, thus identifying it as a susceptibility factor under the influence of epistatic modifiers for the development of autoimmunity.