Lutz H U, Stammler P, Fasler S
Laboratory for Biochemistry, Swiss Federal Institute of Technology, ETH-Zentrum, Zurich.
J Biol Chem. 1993 Aug 15;268(23):17418-26.
Naturally occurring anti-band 3 antibodies appear to have tissue homeostatic functions in the clearance of senescent red cells and in eliciting selective phagocytosis of oxidatively stressed red cells by mediating C3b deposition under conditions that favor the alternative complement pathway (Lutz, H. U., Bussolino, F., Flepp, R., Fasler, S., Stammler, P., Kazatchkine, M. D., and Arese, P. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7368-7372). They overcome the notoriously low affinities of naturally occurring antibodies by having affinity for C3 which renders these antibodies preferred targets of nascent C3b. Anti-band 3 antibodies preferentially formed covalently linked C3b-IgG complexes, when C3 was activated randomly by trypsin. IgG depleted of anti-band 3 antibodies had almost lost the ability to form C3b-IgG complexes. Likewise, anti-band 3 antibodies, but not anti-spectrin antibodies, preferentially formed C3b-IgG complexes on oxidatively stressed red cells in the presence of a 10(3)-fold excess of other serum IgG, when complement deposition was initiated by antibody binding in diluted serum. Moreover, anti-band 3 antibodies preferentially formed C3b-IgG complexes at a 10(5)-fold excess of other IgG on in vivo aging red cells, since C3b-IgG complexes from senescent red cells contained exclusively anti-band 3 antibodies with an affinity for C3. Thus, the low titer, low affinity naturally occurring antibody became functionally relevant by preferred generation of C3b-IgG complexes that can nucleate alternative complement pathway C3 convertases and represent the most effective opsonins (Fries, L. F., Siwik, S. A., Malbran, A., and Frank, M. M. (1987) Immunology 62, 45-51).
天然存在的抗带3抗体似乎在衰老红细胞的清除以及通过在有利于替代补体途径的条件下介导C3b沉积来引发氧化应激红细胞的选择性吞噬方面具有组织稳态功能（Lutz, H. U., Bussolino, F., Flepp, R., Fasler, S., Stammler, P., Kazatchkine, M. D., and Arese, P. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7368 - 7372）。它们通过对C3具有亲和力来克服天然存在抗体众所周知的低亲和力，这使得这些抗体成为新生C3b的优先靶点。当C3被胰蛋白酶随机激活时，抗带3抗体优先形成共价连接的C3b-IgG复合物。去除抗带3抗体的IgG几乎丧失了形成C3b-IgG复合物的能力。同样，当在稀释血清中通过抗体结合启动补体沉积时，在存在10³倍过量的其他血清IgG的情况下，抗带3抗体而非抗血影蛋白抗体优先在氧化应激红细胞上形成C3b-IgG复合物。此外，抗带3抗体在体内衰老红细胞上存在10⁵倍过量的其他IgG时优先形成C3b-IgG复合物，因为来自衰老红细胞的C3b-IgG复合物仅包含对C3具有亲和力的抗带3抗体。因此，这种低滴度、低亲和力的天然存在抗体通过优先产生能够启动替代补体途径C3转化酶并代表最有效调理素的C3b-IgG复合物而在功能上变得相关（Fries, L. F., Siwik, S. A., Malbran, A., and Frank, M. M. (1987) Immunology 62, 45 - 51）。
