Youd Michele E, Ferguson Andrew R, Corley Ronald B
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Eur J Immunol. 2002 Aug;32(8):2328-37. doi: 10.1002/1521-4141(200208)32:8<2328::AID-IMMU2328>3.0.CO;2-T.
We have investigated the roles of IgM and complement (C) in the enhancement of primary immune responses and the localization of protein antigen (Ag) in the spleen. Pentameric but not monomeric IgM enhances antibody (Ab) responses in both wild-type and secretory micro-deficient (micro(s) (-/-)) mice, indicating that a single IgM clone is sufficient as long as it activates C. Ag localizes on follicular dendritic cells (FDC) within 16 h after injection of immune complexes (IC) containing pentameric but not monomeric IgM. Surprisingly, pentameric IgM-containing IC were trapped in spleens of C3-depleted and Cr2-deficient mice. However, the IC were found only in the marginal zone (MZ), associated predominantly with MZ macrophages. IC were also detected in the MZ in normal mice within 1 h after injection, but associated with other cells in addition to MZ macrophages. The results demonstrate an important role for pentameric IgM in the initiation of Ag trapping, a step independent of C3 activation and of the interaction of IC with CR1 and CR2. The data also provide direct evidence that C3 activation is required for the next phase of localization, in which Ag moves from the MZ to FDC, with consequent enhancement of specific immune responses.
我们研究了IgM和补体（C）在增强初次免疫反应以及蛋白质抗原（Ag）在脾脏中的定位方面的作用。五聚体而非单体IgM可增强野生型和分泌型微缺陷（micro(s) (-/-)）小鼠的抗体（Ab）反应，这表明只要激活补体，单个IgM克隆就足够了。在注射含有五聚体而非单体IgM的免疫复合物（IC）后16小时内，Ag定位于滤泡树突状细胞（FDC）上。令人惊讶的是，含有五聚体IgM的IC被困在C3缺陷和Cr2缺陷小鼠的脾脏中。然而，IC仅在边缘区（MZ）被发现，主要与MZ巨噬细胞相关。在正常小鼠中，注射后1小时内也在MZ中检测到IC，但除了MZ巨噬细胞外还与其他细胞相关。结果表明五聚体IgM在Ag捕获的起始中起重要作用，这一步骤独立于C3激活以及IC与CR1和CR2的相互作用。数据还提供了直接证据，表明C3激活是定位下一阶段所必需的，在该阶段Ag从MZ转移到FDC，从而增强特异性免疫反应。
