Fischer M B, Ma M, Goerg S, Zhou X, Xia J, Finco O, Han S, Kelsoe G, Howard R G, Rothstein T L, Kremmer E, Rosen F S, Carroll M C
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 1996 Jul 15;157(2):549-56.
Mice deficient in complement components C3 (C3 -/-) and C4 (C4 -/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage (phi X174). Characterization of the deficient mice demonstrated a diminished level of peanut agglutinin+ germinal centers and a failure in isotype switching despite normal B cell signaling in vitro. The nature of the defect was found to lie at the B cell level, as the T cells were primed in C3- and C4-deficient mice as well as those in wild-type mice. These results, and the finding that the defect could be partly reversed by a 10-fold increase in Ag dose, support the hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity.
研究发现，缺乏补体成分C3（C3 -/-）和C4（C4 -/-）的小鼠对T细胞依赖性抗原（噬菌体（phi X174））的抗体反应存在严重缺陷。对缺陷小鼠的特征分析表明，花生凝集素阳性生发中心水平降低，尽管体外B细胞信号传导正常，但同种型转换失败。由于T细胞在C3和C4缺陷小鼠以及野生型小鼠中均能被激活，因此发现缺陷的本质在于B细胞水平。这些结果，以及抗原剂量增加10倍可部分逆转缺陷这一发现，支持了以下假设：补体配体，即C3b和C3d与抗原-抗体复合物的共价结合会增加其免疫原性。
