MacGill T C, MacGill R S, Casadevall A, Kozel T R
Department of Microbiology and Cell and Molecular Biology Program, School of Medicine, University of Nevada, Reno, NV 89557, USA.
J Immunol. 2000 May 1;164(9):4835-42. doi: 10.4049/jimmunol.164.9.4835.
The capsular swelling or quellung reaction was reported almost 100 years ago and described the effect of Abs on the appearance of microbial capsules. Despite widespread use to assess Ab binding to capsules, relatively little is known as to the mechanism of this effect or its biological consequences. The fungus Cryptococcus neoformans is an attractive system to study capsule reactions because it has a large polysaccharide capsule that is readily visible by light microscopy. When viewed by differential interference contrast microscopy, binding of mAb to C. neoformans cells produced two distinct capsular reactions that depended on the Ab epitope specificity and the yeast serotype. In the first pattern, termed "rim," the capsule appears transparent with a highly refractive outer edge. In the second pattern, termed "puffy," the capsule appears opaque and lacks a highly refractive outer rim. mAbs that bind with a rim pattern suppress the overall rate of C3 deposition on the yeast via the classical and alternative complement pathways. In contrast, mAbs that bind with a puffy pattern do not affect C3 deposition. Protective and nonprotective IgM mAbs produce rim and puffy patterns, respectively. These results indicate that: 1) capsule reactions are a consequence of Ab-induced changes in capsular refractive index; 2) the type of capsule reaction depends on the Ab specificity; and 3) Ab-induced changes in refractive index correlate with biological activities important for host defense against C. neoformans. Our results provide the first evidence associating distinct capsule reaction patterns with Ab biological activity.
荚膜肿胀或荚膜肿胀反应在近100年前就有报道，描述了抗体对微生物荚膜外观的影响。尽管广泛用于评估抗体与荚膜的结合，但对于这种效应的机制或其生物学后果却知之甚少。新型隐球菌是研究荚膜反应的一个有吸引力的系统，因为它有一个大的多糖荚膜，在光学显微镜下很容易看到。用微分干涉相差显微镜观察时，单克隆抗体与新型隐球菌细胞的结合产生了两种不同的荚膜反应，这取决于抗体的表位特异性和酵母血清型。在第一种模式中，称为“边缘”模式，荚膜看起来是透明的，有一个高折射的外边缘。在第二种模式中，称为“蓬松”模式，荚膜看起来是不透明的，没有高折射的外缘。以边缘模式结合的单克隆抗体通过经典和替代补体途径抑制C3在酵母上的总体沉积速率。相比之下，以蓬松模式结合的单克隆抗体不影响C3沉积。保护性和非保护性IgM单克隆抗体分别产生边缘和蓬松模式。这些结果表明：1）荚膜反应是抗体诱导的荚膜折射率变化的结果；2）荚膜反应的类型取决于抗体的特异性；3）抗体诱导的折射率变化与宿主抵御新型隐球菌的重要生物学活性相关。我们的结果提供了第一个将不同的荚膜反应模式与抗体生物学活性相关联的证据。
