Transfer of human serum IgG to nonobese diabetic Igμnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome
Transfer of human serum IgG to nonobese diabetic Igμnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome
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DOI：
10.1073/pnas.95.13.7538
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Humphreys-Beher, MG
中科院分区：
文献类型：
--
作者：
Robinson, CP;Brayer, J;Humphreys-Beher, MG
NOD（非肥胖型糖尿病）小鼠已被研究为自身免疫性胰岛素依赖性糖尿病和舍格伦综合征的动物模型。NOD.IG mu（null）小鼠缺乏功能性B淋巴细胞，与NOD小鼠相似，但没有自身免疫性胰岛炎和糖尿病，其下颌下腺和泪腺发生进行性组织病理学损伤。尽管T细胞在唾液和泪腺组织中的局部外观，NOD.IG mu（null）小鼠不能失去分泌功能，这是通过激动剂毛果芸香碱刺激毒蕈碱/胆碱能受体确定的，表明B细胞自身抗体在介导外分泌干燥中的作用。输注来自亲代NOD小鼠或人类原发性舍格伦综合征患者的纯化血清IgG或F（ab '）（2）片段，但不输注来自健康对照的血清IgG，改变刺激的唾液产生，这一观察结果与抗体与神经受体的结合一致。此外，人类患者IgE组分竞争性抑制毒蕈碱受体激动剂[H-3]奎宁环基二苯乙酸酯与唾液腺膜的结合。这种自身抗体活性在用完整唾液细胞预吸附后丧失。这些发现表明，自身抗体在与干燥综合征的自身免疫性外分泌病有关的分泌过程的功能障碍中起重要作用。
The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjogren's syndrome, NOD.Ig mu(null) mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Ig mu(null) mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')(2) fragments from parental NOD mice or human primary Sjogren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors, Furthermore, human patient Ige fractions competitively inhibited the binding of the muscarinic receptor agonist, [H-3]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjogren's syndrome.