Suppressive Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on the High-Affinity Antibody Response in C57BL/6 Mice

作者：K. Inouye, Tomohiro Ito, Hidekazu Fujimaki, Yoshimasa Takahashi, Toshitada Takemori, Xiaoqing Pan, Chiharu Tohyama, Keiko Nohara · 发表于：Toxicological Sciences · 年份：2003 · DOI：10.1093/toxsci/kfg132 · 被引用次数：28 · 研究领域：Toxic Organic Pollutants Impact、Immunotoxicology and immune responses、Carcinogens and Genotoxicity Assessment

In the humoral immune response to an invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG-class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In this paper we investigate the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 microg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on day 0. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was evaluated until day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from day 7 until day 14. In TCDD-administered mice, on day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high-affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4...