Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. III. Absence in nu/nu mice: evidence for T-cell dependence of the anti-idiotypic-antibody response.

Abstract

In previous papers (1, 2) in this series we have presented evidence that an autoanti-idiotypic-antibody response occurs during the normal immune response to a Tindependent antigen. The evidence also suggested that this auto-anti-idiotypic response is involved in the regulation of the immune response. It was established that hapten-augmentable plaque-forming cells (PFC),I defined as antibody-producing cells which could not be detected as PFC in the Jerne assay unless hapten was present during the assay, represented cells whose secretion of antibody was inhibited by bound auto-anti-idiotypic antibody. Furthermore, it was shown that anti-idiotypic antibody can be assayed by its ability to cause hapten-reversible inhibition of plaque formation.In these earlier studies (1, 2) we noted that the magnitude of the response to trinitrophenyl-lys-Ficoll (TNP-F) falls precipitously between days 4 and 7 after immunization in both AKR/J and BALB/c mice (1, 2) and that serum from AKR/ J mice taken 7 d after injection of TNP-F contained anti-idiotypic antibody to antitrinitrophenyl (TNP). An important role for anti-idiotypic antibody in the down regulation of the anti-TNP response was suggested by the presence of haptenaugmentable PFC in spleens taken more than 4 d after immunization. The percentage of hapten-augmentable (anti-idiotype-blocked) PFC arising spontaneously during the immune response to TNP-F in AKR/J mice was 5% on day 4 and 25% on day 5. Moreover, normal AKR/J recipients of syngeneic TNP-F-immune spleen cells plus antigen had a far higher incidence of hapten-augmentable PFC 3 and 4 d after cell transfer (298 and 122%, respectively). The PFC response by such recipients, as detected in the absence of hapten, was lower than that of recipients of normal cells; however, the results of the assay in the presence of hapten showed this apparent decrease to be a result of the blocking of large numbers of PFC by anti-idiotypic

Immunoresponses to Neisseria meningitidis epitopes: in vivo analysis of immunocompetent cells involved in suppression of secondary response to phosphorylcholine

“…The augmentable PFCs, which are responsible for the overshooting, have in most cases been shown to be terminally differentiated B cells which are blocked by auto-anti-idiotypic (auto-antiid) antibodies attached to their surface [9,20,48]. Evidence exists that auto-antiid B cells are under T helper (Th) control [2,21,24,28,49,53], and therefore it dan reasonably be hypothesized that priming hosts with NMB triggers a mechanism that activates Ta cells specific for those B cells which produce anti-id antibodies. These B cells, according to the network theory [27], are internal images of the antigen and bind anti-PC antibodies.…”

The idiotype connection: linking infection and multiple sclerosis

“…The theory was initially restricted to Ig and B cells. However, thymectomized and nude mice failed to produce anti-Id antibodies upon immunization with Id + Ig [58,59], demonstrating that Ig molecules are T-cell dependent antigens. Thus, extracellular Ig is endocytosed and processed by APC, and Id-peptides are presented on MHC class II molecules to Id-specific CD4 + T cells [9,13,7,60].…”

T cell regulation of IgG subclass antibody production in response to T-independent antigens.

“…Recent studies (29) have suggested that this might be the result of T cell-dependent anti-idiotype-induced regulation of the TNP-Ficoll response.…”