Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation.

Abstract

We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions.

Specificity and cross‐reactive idiotypes of anti‐glomerular basement membrane autoantibodies in HgCl2‐induced autoimmune glomerulonephritis

“…Id have been localized in glomerular immune deposits of LPS-injected mice [37] and of SLE patients [38]. In the mercury model, the CRIdl5 could not be revealed on kidney sections suggesting that it was located close to the antigen-combining site.…”

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

“…Furthermore, only 1% or less of the total immunoglobulin secreted by the cultured spleen cells had the H130 idiotype, even in old MRL/lpr mice, whereas in MRL/lpr sera the H130 idiotype constitutes up to 28% (mean 10%) of total serum immunoglobulin (7). A similar discrepancy between serum levels and in vitro synthesis of a major crossreactive idiotype (CRI) occurs in the anti-p-azobenzenearsonate response of A/J mice (13 (16) and is also inducible by LPS stimulation of B cells (17). Polyclonal B cell activation can, therefore, induce expression of apparently unrelated germ-line V genes.…”

Antigen size influences the type of glomerular pathology in chronic serum sickness

“…HulgG and HulgM, is that they have an antibodylike structure. In general, during glomerulonephritis immune complexes might be present within immune deposits formed by specific antigenic determinants on the IgG molecules and by anti-idiotype antibodies [36]. In this way, various antibodies with different size and charge, acting as planted antigens, might constitute a target for an anti-idiotypic immune response.…”