受体选择与B细胞自身免疫耐受

Receptor Selection and B Cell Immune Tolerance

基因重组机制的存在使得B细胞抗原受体呈现高度的多态性,这其中包括大量的自身反应性抗原受体;而免疫细胞在发育过程中对自身抗原耐受状态的形成正是为了避免对机体自身的攻击。传统认为这主要缘于自身反应性细胞或克隆的死亡性清除,即细胞选择;近年来随基因操作技术特别是转基因及基因靶导技术的成熟运用,发现这些被“清除”的细胞并非全部死亡,其中大部分是通过重新启动基因重组机制以一种“受体选择”(Receptor selection)的方式,以重组的新的非自身反应性受体替代了原自身反应性受体;同时受体选择尚参与成熟B特异性的调整,以使正参与免疫反应B细胞受体更加多样化从而适应当前免疫应答的需要。

The immune system of mammalian has developed sophisticated mechanism to deal with diverse unknown antigens by random rearrangement of V, D and J antigen gene fragments. The immune self-tolerance is the mechanism to avoid self-destructlon by the gene rearrangement generated autoreactive lymphocytes. Until recently it was believed that autoreactive lymphOcytes are either deleted or rendered unable to respond by the supposed cell or clone selection mechanism. However, recent findings from a number of laboratories suggest instead of cell selection but receptor selection plays an essential role in immune self-tolerance. Receptor selection is carried out by secondary or nested rearrangement of antigen receptor gene fragments, and can occur at different stages of lymphocyte differentiation. Furthermore, secondary rearrangement of receptor gene also plays an important role in shaping immune response after the interaction of receptor with antigen by altering its specificity.