Polyspecific and autoreactive IgA secreted by hybridomas derived from Peyer's patches of vomitoxin-fed mice: characterization and possible pathogenic role in IgA nephropathy.
Polyspecific and autoreactive IgA secreted by hybridomas derived from Peyer's patches of vomitoxin-fed mice: characterization and possible pathogenic role in IgA nephropathy.
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呕吐毒素喂养小鼠派尔氏集结衍生的杂交瘤分泌的多特异性和自身反应性 IgA：IgA 肾病的特征和可能的致病作用。
DOI：
10.1016/0278-6915(94)90072-8
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Pestka,JJ
中科院分区：
文献类型：
--
作者：
Rasooly,L;Abouzied,MM;Brooks,KH;Pestka,JJ
从喂了呕吐毒素的BALB/c小鼠Peyer’s斑块中分离到122个产生免疫球蛋白（Ig）A的杂交瘤克隆，并对所产生的抗体进行了抗原特异性和致病性鉴定。当对DNA、鞘磷脂、甲状腺球蛋白、胶原蛋白、酪蛋白、心磷脂和牛血清白蛋白偶联物（代表自身和非自身抗原）进行反应性测试时，大约95%的单克隆IgAs与至少一种抗原结合，80%与一种以上抗原结合。通过证明一种抗原能够抑制单克隆IgA与另一种抗原的结合，进一步表明了一些单克隆IgA的多特异性。梯度天然聚丙烯酰胺凝胶的蛋白染色和Western blotting结果表明，分离的单克隆IgA以三聚体为主。反复注射具有代表性的单克隆IgAs的小鼠在四个被测试的克隆中有三个诱导微血尿，但在肾小球中没有IgA沉积。此外，4种单克隆IgAs中有3种引起肾系膜中IgG和C3的沉积。这些和先前的结果表明，饮食中的呕吐毒素在Peyer’s patch水平上促进IgA分泌B细胞的多克隆激活和扩增，由此产生的多特异性、自身反应性IgA可能有助于肾脏的发病。
A total of 122 immunoglobulin (Ig)A-producing hybridoma clones were isolated from the Peyer's patches of vomitoxin-fed BALB/c mice and the resultant antibodies were characterized for their antigenic specificity and pathogenic potential. When reactivity was tested against a panel consisting of DNA, sphingomyelin, thyroglobulin, collagen, casein, cardiolipin and bovine serum albumin conjugates of phosphorylcholine, inulin and trinitrophenol that were representative of self and non-self antigens, approximately 95% of the monoclonal IgAs bound to at least one of the panel antigens and 80% bound to more than one antigen. The polyspecificity of some of the monoclonal IgAs was further suggested by demonstrating the capacity of one antigen to inhibit binding of monoclonal IgA to another antigen. Protein staining and Western blotting of gradient native polyacrylamide gels, indicated that trimeric IgA predominated in the isolated monoclonal IgAs. Repeated injections of mice with representative monoclonal IgAs induced microhaematuria in three of four of the clones tested but not IgA deposition in the kidney glomerulus. In addition, three of the four monoclonal IgAs caused IgG and C3 deposition in the kidney mesangium. These and previous results suggest that dietary vomitoxin promotes the polyclonal activation and expansion of IgA-secreting B cells at the Peyer's patch level and that resultant polyspecific, autoreactive IgA may contribute to kidney pathogenesis.