Rosenblatt N, Hartmann K U, Loor F
Laboratoire d'Immunologie, Université Louis Pasteur, Strasbourg, France.
Autoimmunity. 1995;20(1):9-18. doi: 10.3109/08916939508993334.
The murine gld mutation is targetted to the gene coding for the ligand of the Fas receptor for apoptosis. Gld mice display a lymphoproliferative and autoimmune syndrome that can be transferred in both irradiated euthymic wild and athymic beige (nubg) recipients. In order to test whether a supply of normal wild cells could correct the development of the gld syndrome, nubg mice were grafted with mixtures of gld and wild spleen cells from congenic donors which differed for the allotypes of the T-cell Thy1 membrane glycoprotein and/or of the B-cell Ig heavy chain. In the nubg chimeras, the wild spleen cells could down-regulate the hyperactivation of the B cells and the proliferation of the gld T cells, but this was not due to total eradication of the gld T-cell subset. Since this occurred in an athymic recipient, the correction of the gld syndrome did not require wild stem cell differentiation within a thymic environment, but should only depend on a sufficient Fas ligand supply by normal wild cells. Since the gld cells could proliferate in the nubg environment, the nubg environment could not provide sufficient Fas ligand to regulate the gld cell proliferation. Thus, the nubg B cells might lack Fas ligand expression, or express it but to a lower extent that T cells.
小鼠的gld突变作用于编码凋亡的Fas受体配体的基因。gld小鼠表现出一种淋巴细胞增生和自身免疫综合征，这种综合征可在经辐射的正常野生型和无胸腺米色（nubg）受体中传递。为了测试正常野生细胞的供应是否能纠正gld综合征的发展，将来自同基因供体的gld和野生脾细胞混合物移植到nubg小鼠体内，这些供体在T细胞Thy1膜糖蛋白和/或B细胞Ig重链的同种异型上有所不同。在nubg嵌合体中，野生脾细胞可以下调B细胞的过度激活和gld T细胞的增殖，但这并不是由于gld T细胞亚群的完全根除。由于这发生在无胸腺受体中，gld综合征的纠正并不需要野生干细胞在胸腺环境中分化，而只应取决于正常野生细胞提供足够的Fas配体。由于gld细胞可以在nubg环境中增殖，nubg环境无法提供足够的Fas配体来调节gld细胞的增殖。因此，nubg B细胞可能缺乏Fas配体表达，或者表达但程度低于T细胞。
