Brown E J, Joiner K A, Gaither T A, Hammer C H, Frank M M
J Immunol. 1983 Jul;131(1):409-15.
Pneumococcal cell walls are potent activators of the alternative complement (C) pathway; pneumococcal capsules are not. C3b that is deposited onto the cell walls of encapsulated organisms, however, functions inefficiently in host defense compared to C3b deposited onto capsular polysaccharides. Results of previous studies with guinea pig erythrocytes suggested that C3b deposited onto surfaces that do not activate the alternative pathway is rapidly inactivated. In the present study, we examined the interactions of C3b bound to pneumococcal capsules, to pneumococcal cell walls, and to the surface of sheep erythrocytes (E) with the serum control proteins, Factor H (beta 1H globulin) (H) and Factor I (C3b/4b inactivator) (I), and with Factor B (B) of the alternative C pathway. Conversion of bound C3b to C3bi was assayed by binding of radiolabeled conglutinin in a quantitative binding assay. Neither pneumococcal cell wall C3b nor capsular C3b was converted efficiently to a conglutinin-binding form by serum incubation. Experiments with purified C components showed that, after incubation with H and I, fewer conglutinin-binding sites were created on pneumococci than on E bearing equal numbers of C3b. Molecular analysis demonstrated that this did not result from cleavage of pneumococcal-bound C3b to an unusual, nonconglutinin-binding form of the molecule. Binding studies in which radiolabeled H was used demonstrated that the majority of C3b that is bound to both pneumococcal capsules and cell walls bound H with a lower affinity than did E-bound C3b. Studies of the binding of radiolabeled B demonstrated that C3b that was bound to pneumococcal cell walls and to E demonstrated equal affinity for B. In contrast, the majority of C3b that was fixed to pneumococcal capsules bound B with only 1/30 as high affinity. We conclude that pneumococcal capsules are not alternative pathway activators because the low affinity of capsular C3b for B leads to inefficient formation of an alternative pathway convertase, C3bBb. With regard to H binding, both cell wall- and capsular-bound C3b act as if they were in a "protected site" and resist degradation by the control proteins.
肺炎球菌细胞壁是替代补体（C）途径的有效激活剂；肺炎球菌荚膜则不是。然而，与沉积在荚膜多糖上的C3b相比，沉积在被膜菌细胞壁上的C3b在宿主防御中功能效率较低。先前用豚鼠红细胞进行的研究结果表明，沉积在不激活替代途径的表面上的C3b会迅速失活。在本研究中，我们检测了与肺炎球菌荚膜、肺炎球菌细胞壁以及绵羊红细胞（E）表面结合的C3b与血清对照蛋白H因子（β1H球蛋白）（H）、I因子（C3b/4b灭活剂）（I）以及替代C途径的B因子（B）之间的相互作用。在定量结合试验中，通过放射性标记的胶固素结合来检测结合的C3b向C3bi的转化。血清孵育后，肺炎球菌细胞壁C3b和荚膜C3b均未有效地转化为胶固素结合形式。用纯化的C成分进行的实验表明，与H和I孵育后，肺炎球菌上产生的胶固素结合位点比具有相同数量C3b的E上产生的少。分子分析表明，这并非由于肺炎球菌结合的C3b裂解为分子的一种不寻常的、非胶固素结合形式所致。使用放射性标记的H进行的结合研究表明，与肺炎球菌荚膜和细胞壁结合的大多数C3b与H的结合亲和力低于与E结合的C3b。放射性标记的B结合研究表明，与肺炎球菌细胞壁和E结合的C3b对B的亲和力相等。相比之下，固定在肺炎球菌荚膜上的大多数C3b与B的结合亲和力仅为其1/30。我们得出结论，肺炎球菌荚膜不是替代途径激活剂，因为荚膜C3b对B的低亲和力导致替代途径转化酶C3bBb的形成效率低下。关于H结合，细胞壁结合的C3b和荚膜结合的C3b的行为就好像它们处于一个“受保护位点”，并抵抗对照蛋白的降解。
