Spitzer R E, Stitzel A E, Tsokos G C
Department of Pediatrics, State University of New York Health Science Center, Syracuse 13210.
J Immunol. 1992 Jan 1;148(1):137-41.
In an effort to understand the development and control of autoantibody production, we studied the affinity of autoantibody to the alternative pathway C3/C5 convertase (C3 nephritic factor (C3NeF)) and its autoanti-idiotypic antibodies, Ab2 alpha and Ab2 beta. These were isolated and purified from newborns, normal adults, and patients with membranoproliferative glomerulonephritis. In all cases, both IgG and IgM C3NeF were available for study. The affinity of IgG and IgM C3NeF for their natural Ag (10(8) liters/mol) as well as for the internal image of that Ag displayed on Ab2 beta was high (10(10) liters/mol). Furthermore, the affinity of IgG C3NeF was nearly 100-fold higher in patients than in newborns, whereas there were no significant changes with IgM C3NeF. By contrast, there were not differences in the affinity of IgG Ab2 alpha (which does not display any likeness to the native Ag) from normal adults and patients to any C3NeF isolate. There was, however, a progressive increase in affinity between both Ab2 alpha preparations and IgG C3NeF from newborns, adult normal subjects, and patients, implying an alteration in C3NeF to account for the changes in affinity. These data suggest that Ag-driven affinity maturation occurs with autoantibody but may not occur within the idiotypic network. These data also indicate that as autoantibody affinity matures, it appears to modify its idiotype, perhaps in an effort towards autoregulation.
为了了解自身抗体产生的发展和调控，我们研究了自身抗体与替代途径C3/C5转化酶（C3肾炎因子（C3NeF））及其自身抗独特型抗体Ab2α和Ab2β的亲和力。这些抗体从新生儿、正常成年人以及膜增生性肾小球肾炎患者中分离和纯化得到。在所有情况下，IgG和IgM C3NeF均可用于研究。IgG和IgM C3NeF对其天然抗原（10⁸升/摩尔）以及在Ab2β上展示的该抗原内影像的亲和力都很高（10¹⁰升/摩尔）。此外，患者体内IgG C3NeF的亲和力比新生儿高近100倍，而IgM C3NeF则没有显著变化。相比之下，正常成年人和患者的IgG Ab2α（与天然抗原没有任何相似性）对任何C3NeF分离物的亲和力没有差异。然而，来自新生儿、成年正常受试者和患者的两种Ab2α制剂与IgG C3NeF之间的亲和力逐渐增加，这意味着C3NeF发生了改变以解释亲和力的变化。这些数据表明，自身抗体存在抗原驱动的亲和力成熟，但在独特型网络内可能不会发生。这些数据还表明，随着自身抗体亲和力的成熟，它似乎会改变其独特型，这可能是一种自我调节的努力。
