Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris
Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris
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DOI：
10.1002/1521-4141(200203)32:3
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发表时间：
2002-03
影响因子：
5.4
通讯作者：
K. Tsunoda;T. Ota;Harumi Suzuki;M. Ohyama;T. Nagai;T. Nishikawa;M. Amagai;S. Koyasu
中科院分区：
文献类型：
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作者：
K. Tsunoda;T. Ota;Harumi Suzuki;M. Ohyama;T. Nagai;T. Nishikawa;M. Amagai;S. Koyasu
寻常型天疱疮(PV)患者产生致病性抗Dsg3自身抗体的患者对桥粒芯糖蛋白3(Dsg3)的耐受破坏机制尚不清楚。在这项研究中，使用一种新的包括Dsg3基因敲除小鼠的PV小鼠模型，我们研究了导致产生针对Dsg3的自身抗体的机制。将重组小鼠Dsg3免疫的Dsg3-/-脾细胞过继转移到表达Dsg3的Rag2/-受体小鼠，可稳定产生抗Dsg3-Ig G，并形成包括口腔糜烂伴基底上棘层松解在内的PV表型。从Dsg3-/-、Dsg3+/-或Dsg3+/+小鼠分离的T细胞和B细胞与不同的组合混合后，仅与Dsg3-/-T细胞和Dsg3-/-B细胞混合，而与其他组合不产生致病性抗Dsg3免疫球蛋白G。这些结果表明，B细胞和T细胞对Dsg3的耐受性丧失在PV自身免疫状态的发展中起重要作用。
Mechanisms of tolerance break against desmoglein 3 (Dsg3) in patients with pemphigus vulgaris (PV) producing pathogenic anti‐Dsg3 IgG autoantibodies are unclear. In this study, using a novel PV mouse model involving Dsg3 knockout mice, we investigated the mechanisms leading to production of autoantibodies against Dsg3. Adoptive transfer of Dsg3–/– splenocytes immunized with recombinant mouse Dsg3 to Rag2–/– recipient mice expressing Dsg3 resulted in the stable production of anti‐Dsg3 IgG and development of PV phenotypes including oral erosions with suprabasilar acantholysis. When purified T and B cells from Dsg3–/–, Dsg3+/– or Dsg3+/+ mice were mixed with various combinations and transferred to Rag2–/– mice, pathogenic anti‐Dsg3 IgG production was observed only with a combination of Dsg3–/– T and Dsg3–/– B cells but not with the other combinations. These results suggest that loss of tolerance against Dsg3 in both B and T cells is important for the development of autoimmune state of PV.