PREVENTION OF AUTOIMMUNE SYMPTOMS IN AUTOIMMUNE-PRONE MICE BY ELIMINATION OF B-1 CELLS

PREVENTION OF AUTOIMMUNE SYMPTOMS IN AUTOIMMUNE-PRONE MICE BY ELIMINATION OF B-1 CELLS
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DOI:
10.1093/intimm/7.5.877
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发表时间:
1995-05-01
影响因子:
4.4
通讯作者:
HONJO, T
HONJO, T
中科院分区:
医学3区
文献类型:
--
作者:
MURAKAMI, M;YOSHIOKA, H;HONJO, T

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我们最近对一种自身抗体转基因小鼠系的研究表明,腹膜B-1细胞与自身免疫性症状有关,然而,腹膜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。为了检验腹膜B-1细胞是否参与了自身免疫易感的NZB小鼠的自身免疫症状,我们采用低渗休克的方法,每7天向新生或8周龄的NZB小鼠反复注射蒸馏水,以消除腹膜细胞。通过这种治疗,在腹腔内自我更新的B-1细胞有望被优先清除,而其他腹膜细胞在这种治疗后可以很容易地从骨髓中供应。事实上,在蒸馏水处理的老年NZB小鼠中,脾脏和肠道固有层中B-1细胞的数量减少,但常规a细胞和T细胞的数量没有变化,而且,12个月大的NZB小鼠抗红细胞自身抗体的产生显著减少,自身免疫性溶血性贫血的发生减少。同样,通过水注射消除NZB/NZW (NZB/W) F-1小鼠腹膜细胞可降低血清中抗dna IgG抗体,减轻肾脏病理变化,这些结果提示腹膜B-1细胞可能是NZB和NZB/W F-1小鼠自身免疫性疾病中产生自身抗体的细胞的来源。
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 a 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) F-1 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 F-1 mice.