Humphrey J H
Eur J Immunol. 1981 Mar;11(3):212-20. doi: 10.1002/eji.1830110310.
Dinitrophenylated (DNP) conjugates of Ficoll, hydroxyethyl starch, levan, dextran, type 3 pneumococcal capsular polysaccharide SIII, pectin, alginic and hyaluronic acid at various epitope densities were tested for their capacity to inhibit secondary IgG anti-DNP antibody responses using an in vivo transfer system. Some aminobenzylarsonate conjugates were examined similarly. Conjugates of the acidic polysaccharides were markedly more effective than those of uncharged polysaccharides. Conjugated with high epitope densities were particularly tolerogenic. DNP conjugates of Ficoll and hydroxyethyl starch elicited prolonged IgM responses over a wide dose range, and there are indications in the literature that conjugates of dextran do likewise. All the polysaccharide conjugates, labeled with radioiodine, persisted in the body for long periods (half-lives 8.5--63 days), and all were cleared rapidly from, but remained detectable in the blood for many days. Gross tissue distributions varied markedly from one conjugate to another, and autoradiography revealed unexpected differences in cellular localization. Despite substantial retention in the liver, some uncharged polysaccharides were localized only in parenchymal and not in Kupffer cells. In the spleen, only the acidic polysaccharides were predominantly localized in red pulp macrophages, and the neural polysaccharides were detectable exclusively, and in the case of Ficoll, hydroxyethyl starch and some dextrans very intensely in macrophages of the marginal zone of the white pulp. It is suggested that retention of thymus-independent antigens in marginal-zone macrophages favors, whereas trapping in red-pulp macrophages diminishes immunogenicity, and that tolerogenic effectiveness depends upon a balance between tolerization of B cells by free antigen and stimulation by antigen presented by marginal-zone macrophages. The distinction between functionally different macrophages in the spleen is elaborated in the following report.
使用体内转移系统，测试了不同表位密度下的菲可（Ficoll）、羟乙基淀粉、左聚糖、右旋糖酐、3型肺炎球菌荚膜多糖SIII、果胶、海藻酸和透明质酸的二硝基苯基化（DNP）缀合物抑制继发性IgG抗DNP抗体反应的能力。对一些氨基苯胂酸盐缀合物也进行了类似检查。酸性多糖的缀合物比不带电荷的多糖缀合物明显更有效。高表位密度的缀合物尤其具有耐受性。菲可和羟乙基淀粉的DNP缀合物在很宽的剂量范围内引发了延长的IgM反应，并且文献中有迹象表明右旋糖酐的缀合物也有同样的情况。所有用放射性碘标记的多糖缀合物在体内长期存在（半衰期8.5 - 63天），并且都迅速从血液中清除，但在血液中仍可检测到许多天。不同缀合物的总体组织分布差异显著，放射自显影显示细胞定位存在意外差异。尽管在肝脏中有大量滞留，但一些不带电荷的多糖仅定位于实质细胞而非库普弗细胞。在脾脏中，只有酸性多糖主要定位于红髓巨噬细胞，而神经多糖仅在白髓边缘区的巨噬细胞中可检测到，对于菲可、羟乙基淀粉和一些右旋糖酐，在白髓边缘区的巨噬细胞中检测非常强烈。有人提出，边缘区巨噬细胞中胸腺非依赖性抗原的滞留有利于免疫反应，而红髓巨噬细胞中的捕获则会降低免疫原性，并且耐受性有效性取决于游离抗原对B细胞的耐受性与边缘区巨噬细胞呈递的抗原刺激之间的平衡。脾脏中功能不同的巨噬细胞之间的区别在以下报告中详细阐述。
