Murakami M, Yoshioka H, Shirai T, Tsubata T, Honjo T
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Int Immunol. 1995 May;7(5):877-82. doi: 10.1093/intimm/7.5.877.
Our recent studies on an autoantibody-transgenic mouse line demonstrated that peritoneal B-1 cells are responsible for autoimmune symptoms. However, whether B-1 cells in the peritoneum are generally involved in the pathogenesis of autoimmune disease remains controversial. To test the possible involvement of peritoneal B-1 cells in autoimmune symptoms of autoimmune-prone NZB mice, we eliminated the peritoneal cells by hypotonic shock with repeated i.p. injection of distilled water every 7 days into neonatal or 8-week-old NZB mice. By this treatment, B-1 cells, which self-renew within the peritoneal cavity, are expected to be preferentially eliminated, while other peritoneal cells can be easily supplied from bone marrows after this treatment. Indeed, in distilled water-treated old NZB mice, the number of B-1 cells decreased in spleen as well as in lamina propria of the gut but the numbers of conventional B cells and T cells did not change. Moreover, the production of autoantibodies against erythrocytes significantly decreased and the occurrence of autoimmune hemolytic anemia was reduced in 12-month-old treated NZB mice. Similarly, the elimination of peritoneal cells of NZB/NZW (NZB/W) F1 mice by water injection decreased anti-DNA IgG antibodies in the sera and reduced the pathological changes of the kidney. These results suggest that peritoneal B-1 cells may be a source of autoantibody-producing cells in autoimmune diseases of NZB and NZB/W F1 mice.
我们最近对一种自身抗体转基因小鼠品系的研究表明，腹膜B-1细胞是自身免疫症状的起因。然而，腹膜中的B-1细胞是否普遍参与自身免疫性疾病的发病机制仍存在争议。为了测试腹膜B-1细胞可能参与自身免疫易感NZB小鼠的自身免疫症状，我们通过每隔7天向新生或8周龄的NZB小鼠腹腔内重复注射蒸馏水进行低渗休克来清除腹膜细胞。通过这种处理，预计在腹腔内自我更新的B-1细胞会被优先清除，而其他腹膜细胞在这种处理后可以很容易地从骨髓中补充。事实上，在经蒸馏水处理的老龄NZB小鼠中，脾脏以及肠道固有层中的B-1细胞数量减少，但常规B细胞和T细胞的数量没有变化。此外，12月龄经处理的NZB小鼠中，针对红细胞的自身抗体产生显著减少，自身免疫性溶血性贫血的发生率降低。同样，通过注水清除NZB/NZW（NZB/W）F1小鼠的腹膜细胞可降低血清中的抗DNA IgG抗体，并减少肾脏的病理变化。这些结果表明，腹膜B-1细胞可能是NZB和NZB/W F1小鼠自身免疫性疾病中产生自身抗体细胞的来源。
