Fukuyama H, Adachi M, Suematsu S, Miwa K, Suda T, Yoshida N, Nagata S
Department of Genetics, Osaka University Medical School, Suita, Japan.
J Immunol. 1998 Apr 15;160(8):3805-11.
Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter. The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells. The transgenic mice did not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactive or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.
Fas是肿瘤坏死因子受体家族的成员。Fas配体与Fas结合可诱导表达Fas的细胞发生凋亡。Fas在多种细胞中表达，包括胸腺细胞、外周T细胞和活化的B细胞。小鼠lpr突变是Fas的功能丧失性突变。MRL-lpr/lpr小鼠会出现淋巴结病和脾肿大，并产生多种自身抗体，从而导致自身免疫性疾病。在本报告中，我们描述了一种Fas转基因MRL-lpr小鼠品系的建立，其中使用T细胞特异性鼠源lck启动子表达小鼠Fas cDNA。转基因小鼠在胸腺细胞和外周T细胞中表达功能性Fas，但在B细胞中不表达。转基因小鼠没有积累异常T细胞（Thy-1+B220+），但仍积累B细胞（Thy-1-B220+）；它们产生大量免疫球蛋白（IgG1和IgG2a），包括抗DNA抗体，并发展为肾小球肾炎。这些结果表明，自身反应性或活化的B细胞必须通过活化T细胞表达的Fas配体，经由B细胞中表达的Fas被杀死。
