Clearance kinetics, tissue localization and fate of IgA-anti-idiotype complexes.
To determine the influence of anti-idiotypic antibodies on the complementary idiotype (Id), the clearance kinetics, tissue distribution and fate of idiotype-anti-idiotype complexes were investigated in mice. The complexes were prepared by mixing purified radiolabelled monomeric (mIgA) or polymeric IgA (pIgA) with monoclonal anti-T15 idiotype (B39-38). The 24 hr clearance from circulation of intravenously administered mIgA, mIgA-anti-Id complexes, pIgA and pIgA-anti-Id complexes showed three exponential phases. There was no significant difference in the amount, half-life (t 1/2), or organ distribution of mIgA and mIgA-anti-Id during the first two phases. The mIgA-anti-Id complexes were removed at a faster rate (9.2 +/- 0.5 hr) than the mIgA alone (17.7 +/- 1.3 hr) during the third phase. In contrast, anti-Id affected the clearance of pIgA during the first phase whereby 75% of the administered pIgA-anti-Id complexes, compared with 50% of the pIgA, cleared from the circulation with a t 1/2 of 3 min. This rapid removal from circulation was mediated predominantly by the liver, where 66% of pIgA-anti-Id and 40% of pIgA were detected 10 min after administration of the radiolabelled material. In the second phase, pIgA-anti-Id were removed from circulation at a faster rate (t 1/2 = 28 min) than pIgA (t 1/2 = 43 min). During this phase, 1 hr after administration of radiolabelled material, significantly more pIgA-anti-Id than pIgA were localized in the liver, kidneys, skin and spleen. In contrast, the digestive tract contained more pIgA (22%) than pIgA-anti-Id (11%). Analysis of the mIgA-anti-Id and pIgA-anti-Id by gradient polyacrylamide gel electrophoresis indicated that mIgA-anti-Id were composed of small-sized complexes, while intermediate-sized complexes constituted the majority of the pIgA-anti-Id complexes. These results suggest that the modulatory effect of anti-Id on the complementary IgA idiotype is determined largely by the molecular form of the IgA and the size of the Id-anti-Id complexes.
Rifai
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A
Department of Pathology, Rhode Island Hospital, Providence.
Wu
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CG
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000493:pharmacokinetics*; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology* / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers; D014018:Tissue Distribution
D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D011108:Polymers; C049937:anti-IgA; C034639:polymeric IgA