Böttger E C, Hoffmann T, Hadding U, Bitter-Suermann D
J Immunol. 1985 Dec;135(6):4100-7.
To assess the role of complement in the induction of the humoral immune response, we studied the antibody response of guinea pigs genetically deficient in the second component of the classical complement pathway (C2D-GP) to bacteriophage phi X 174--a T cell-dependent antigen--in comparison with normal guinea pigs and C4D-GP, for which a disturbance in induction of antibody response has been described. We were able to establish a clear dose-response relationship: with low doses of antigen (1 X 10(9) PFU/kg), the antibody response of both complement-deficient strains was grossly impaired as compared with normal guinea pigs. After primary immunization, the peak antibody titer was diminished (1 log10) and declined rapidly; after secondary immunization, the diminution became even more distinct. Both complement-deficient strains had unusual secondary antibody responses almost identical to their primary ones, and amplification of antibody titer, as well as regular isotype switch from IgM to IgG, was absent. By increasing the antigen dose (2 X 10(9) PFU/kg), the antibody responses of the complement-deficient guinea pigs tend to normalize, and when high doses of antigen (1 X 10(10) PFU/kg) were used, the behavior of the complement-deficient animals was nearly indistinguishable from that of normal animals. Partial restoration of the immune response was seen when substituting the genetic complement deficiency by giving serum as source of the missing complement component. The important contribution of the C2 deficiency is given by the now compelling evidence that it is not the missing individual component itself, but rather the common block in sequential activation of C3 via the classical pathway in both complement deficiencies, that is responsible for the impaired humoral immune response, especially at low antigen doses. We therefore postulate that an intact classical pathway contributes to reaching a normal humoral immune response.
为了评估补体在诱导体液免疫反应中的作用，我们研究了经典补体途径第二成分基因缺陷的豚鼠（C2D - GP）对噬菌体φX 174（一种T细胞依赖性抗原）的抗体反应，并与正常豚鼠和C4D - GP进行比较，C4D - GP已被描述为在抗体反应诱导方面存在紊乱。我们能够建立明确的剂量反应关系：低剂量抗原（1×10⁹ PFU/kg）时，与正常豚鼠相比，两种补体缺陷品系的抗体反应均严重受损。初次免疫后，抗体峰值滴度降低（1个对数10）且迅速下降；再次免疫后，这种降低变得更加明显。两种补体缺陷品系的二次抗体反应异常，几乎与初次反应相同，不存在抗体滴度的放大以及从IgM到IgG的正常同种型转换。通过增加抗原剂量（2×10⁹ PFU/kg），补体缺陷豚鼠的抗体反应趋于正常化，当使用高剂量抗原（1×10¹⁰ PFU/kg）时，补体缺陷动物的表现与正常动物几乎无法区分。当通过给予血清作为缺失补体成分的来源来替代基因补体缺陷时，可观察到免疫反应的部分恢复。现在有令人信服的证据表明，C2缺陷的重要作用并非缺失的单个成分本身，而是两种补体缺陷中通过经典途径对C3的顺序激活的共同阻断，这导致了体液免疫反应受损，尤其是在低抗原剂量时。因此，我们推测完整的经典途径有助于实现正常的体液免疫反应。
