Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies.
Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies.
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DOI：
10.1084/jem.189.8.1307
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发表时间：
1999-04-19
影响因子：
15.3
通讯作者：
Neuberger, M S
中科院分区：
文献类型：
--
作者：
O'Keefe, T L;Williams, G T;Batista, F D;Neuberger, M S
CD 22是一种B细胞特异性跨膜糖蛋白，其作用是抑制通过B细胞抗原受体（BCR）产生的信号：来自CD 22缺陷小鼠的B细胞在BCR连接时产生增加的Ca 2+通量。在这里，我们表明，这种B细胞高反应性与自身抗体的发展。在8个月大之后，CD 22缺陷小鼠产生针对双链DNA的高滴度血清IgG;这些抗体是多克隆来源的，体细胞突变的，并且具有高亲和力。还注意到心磷脂和髓过氧化物酶抗体滴度增加。结果表明，B淋巴细胞独有的单个基因缺陷，在没有额外的设计的情况下，足以在大比例的老龄动物中引发自身抗体的发展。因此，CD 22可能已经进化到专门调节B细胞触发阈值以避免自身免疫。
CD22 is a B cell–specific transmembrane glycoprotein that acts to dampen signals generated through the B cell antigen receptor (BCR): B cells from CD22-deficient mice give increased Ca2+ fluxes on BCR ligation. Here we show that this B cell hyperresponsiveness correlates with the development of autoantibodies. After the age of eight months, CD22-deficient mice developed high titers of serum IgG directed against double-stranded DNA; these antibodies were of multiclonal origin, somatically mutated, and high affinity. Increased titers of antibodies to cardiolipin and myeloperoxidase were also noted. The results demonstrate that a single gene defect exclusive to B lymphocytes is, without additional contrivance, sufficient to trigger autoantibody development in a large proportion of aging animals. Thus, CD22 might have evolved specifically to regulate B cell triggering thresholds for the avoidance of autoimmunity.