Katz D H, Hamaoka T, Benacerraf B
Proc Natl Acad Sci U S A. 1973 Oct;70(10):2776-80. doi: 10.1073/pnas.70.10.2776.
Administration of the 2,4-dinitrophenyl (Dnp) determinant conjugated to the "nonimmunogenic" copolymer of D-glutamic acid and D-lysine (D-GL) induces Dnp-specific immunological tolerance which is essentially restricted to bone marrow-derived (B) lymphocytes. Previous studies have demonstrated tolerance induction by Dnp-D-GL in predominantly B lymphocytes of the IgG class. The present studies establish and analyze conditions for tolerance induction in Dnp-specific B lymphocytes of the IgE antibody class by taking advantage of: (i) the relatively easy capacity to induce tolerance with Dnp-D-GL in an animal or cell population previously primed to the Dnp determinant; (ii) previously established parameters for the successful adoptive transfer of Dnp-specific IgE antibody responses; and (iii) the capacity to induce, and maintain a state of Dnp-specific tolerance with Dnp-D-GL in adoptive transfer responses. Using these approaches, we have successfully rendered Dnp-specific B cells of the IgE class profoundly and apparently irreversibly tolerant after exposure of such cells to Dnp-D-GL. These observations represent a starting point of wide potential for solving many therapeutic problems concerned with clinical allergies.
将与D-谷氨酸和D-赖氨酸（D-GL）的“非免疫原性”共聚物偶联的2,4-二硝基苯基（Dnp）决定簇进行给药，可诱导Dnp特异性免疫耐受，这种耐受基本上仅限于骨髓来源的（B）淋巴细胞。先前的研究已证明Dnp-D-GL在主要为IgG类的B淋巴细胞中诱导耐受。本研究通过利用以下几点来建立和分析在IgE抗体类的Dnp特异性B淋巴细胞中诱导耐受的条件：（i）在先前已对Dnp决定簇致敏的动物或细胞群体中，用Dnp-D-GL诱导耐受的能力相对容易；（ii）先前建立的成功过继转移Dnp特异性IgE抗体反应的参数；以及（iii）在过继转移反应中用Dnp-D-GL诱导并维持Dnp特异性耐受状态的能力。使用这些方法，我们已成功使IgE类的Dnp特异性B细胞在暴露于Dnp-D-GL后产生深刻且明显不可逆的耐受。这些观察结果是解决许多与临床过敏相关治疗问题的广泛潜在可能性的起点。
