Receptor editing is the main mechanism of B cell tolerance toward membrane antigens
Receptor editing is the main mechanism of B cell tolerance toward membrane antigens
复制标题
DOI：
10.1038/ni1076
复制
发表时间：
2004-06-01
影响因子：
30.5
通讯作者：
Pelanda, R
中科院分区：
文献类型：
--
作者：
Halverson, R;Torres, RM;Pelanda, R
对普遍存在的膜结合自身抗原具有特异性的自身反应性B细胞在骨髓中通过两种耐受机制消除：受体编辑和克隆缺失。然而，在多克隆B细胞群体中，克隆缺失和受体编辑对B细胞耐受性的相对贡献尚未确定。在这里，我们表明，对膜抗原反应性B细胞克隆的耐受性通过受体编辑起作用，细胞损失非常小。受体编辑拯救几乎所有自身反应性B细胞免于缺失的能力依赖于多个连接轻链基因片段作为二级免疫球蛋白轻链基因重排底物的可用性，并且不依赖于自身抗原的亲和力和非自身反应性B细胞的存在。我们的数据进一步表明，克隆缺失是一个默认的途径，只有当受体编辑已经用尽。
Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are eliminated in the bone marrow by two mechanisms of tolerance: receptor editing and clonal deletion. However, the relative contributions of clonal deletion and receptor editing to B cell tolerance in a polyclonal B cell population have not been established. Here we show that tolerance toward a membrane antigen-reactive B cell clone acts by receptor editing with very minimal cell loss. The capacity of receptor editing to rescue almost all autoreactive B cells from deletion relies on the availability of multiple joining light chain gene segments as substrate for secondary immunoglobulin light chain gene rearrangement and is independent of the affinity of the autoantigen and the presence of non-autoreactive B cells. Our data further suggest that clonal deletion is a default pathway that functions only when receptor editing has been exhausted.