Murakami M, Tsubata T, Shinkura R, Nisitani S, Okamoto M, Yoshioka H, Usui T, Miyawaki S, Honjo T
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
J Exp Med. 1994 Jul 1;180(1):111-21. doi: 10.1084/jem.180.1.111.
About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases.
大约一半的抗红细胞自身抗体转基因（autoAb Tg）小鼠患有自身免疫性溶血性贫血，在这些小鼠中，几乎所有的B细胞都可在脾脏、淋巴结和派尔集合淋巴结中检测到，但在腹腔中则检测不到。这种疾病的发生与Tg小鼠中活化的腹腔B-1细胞产生自身抗体密切相关。在本研究中，我们发现口服脂多糖（LPS）可激活健康Tg小鼠肠道固有层以及腹腔中的B-1细胞，并在所有Tg小鼠中诱发自身免疫症状。肠道LPS对腹腔和肠道固有层B-1细胞的激活不仅在抗红细胞自身抗体Tg小鼠和正常小鼠中存在，在先天性缺乏淋巴结和派尔集合淋巴结的aly小鼠中也存在。这些结果表明，这两个部位的B-1细胞可能形成一个独立于派尔集合淋巴结和淋巴结的共同库，并且可以被肠道非胸腺依赖性抗原或多克隆激活剂如LPS激活。肠道LPS通过激活肠道固有层和腹腔中的B-1细胞在Tg小鼠中诱发自身免疫性溶血性贫血，这表明B-1细胞和细菌感染可能在自身免疫性疾病的发病中起致病作用。
