Levels Of Id Research Articles

In vitro production of an anti-DNA idiotype by lymphocytes of normal subjects and patients with systemic lupus erythematosus

We investigated whether normal B cells can synthesize antibodies with an idiotypic marker that occurs with high frequency in anti-DNA antibodies of patients with systemic lupus erythematosus (SLE). This idiotype, Id 16 6 , has been found in the serum of patients with active SLE and in monoclonal anti-DNA antibodies derived from unrelated patients with the disease. We found that cultured lymphocytes of all normal subjects tested produced Id 16 6 when stimulated by pokeweed mitogen (PWM). By contrast, lymphocytes from SLE patients produced Id 16 6 even without mitogenic stimulation, whether or not they were obtained from patients in remission or relapse. Relapsed patients' lymphocytes spontaneously produced the highest levels of Id 16 6 which was found in IgG and IgA, in addition to IgM. The majority of Id 16 6 produced by PWM-stimulated lymphocytes from either normal subjects or patients in remission did not bind to nucleic acid. In relapse, however, the nucleic acid-binding proportion of Id 16 6 rose substantially, indicating that the spontaneously activated B cells in active SLE differ from the subset of B cells that produce Id 16 6 upon PWM stimulation. The findings suggest that the lupus Id 16 6 family is conserved in normal individuals and it consists of two populations of antibodies with different antigenic specificities. The major set is not directed against nucleic acid antigens; its antigenic specificity is unknown and it dominates the Id 16 6 family that appears after PWM stimulation. The other, minor set binds to nucleic acids and becomes prominent in clinically active lupus. These two sets of idiotypically related antibodies may be connected by an immunoregulatory network.

Evidence that anti-idiotype induced immunity to experimental African trypanosomiasis is genetically restricted and requires recognition of combining site-related idiotopes.

The ability of anti-idiotypic (anti-Id) antibodies to immunize mice against African trypanosomiasis independent of antigen has been confirmed. Of three allogeneic anti-Id antibodies raised against three protective monoclonal antibodies, each with specificity for the variant surface antigen of a clone of Trypanosoma rhodesiense, only one (anti-7H11 Id) was effective in immunizing BALB/c mice against homologous challenge. The immunity was associated with the more rapid and enhanced expression of the corresponding Id after infection. The immunity was restricted to mice bearing genes linked to Igh-Ca, which appeared to control expression of this Id both in response to infection and anti-Id treatment. Another Id, 11D5, appeared to be under similar genetic control. Anti-11D5 Id, however, was ineffective in immunizing mice against infection despite inducing high levels of Id bearing molecules before challenge. The immunizing potential of the respective anti-Id antibodies appeared to be related to the relative concentrations of antibodies reactive with idiotopes near to or within the antigen-combining site, which, in turn, determined the relative proportion of Id-bearing clones activated that had antigen binding activity.

Genetic control of the immune response to staphylococcal nuclease. XI. Effects of in vivo administration of anti-idiotypic antibodies.

The effects of prior treatment with heterologous anti-idiotypic antibodies on the response to staphylococcal nuclease (Nase) have been examined. Previous studies have shown that 100% of A/J mice treated with Nase in completes Freund's adjuvant produce anti-Nase antibodies possessing a characteristic idiotype (Id). Mice treated with anti-Id antibodies followed by Nase produced levels of Id equal to or greater than those of control animals treated with Nase alone. The appearance of Id in treated mice preceded the appearance of anti-Nase activity, and animals treated with anti-Id alone produced high levels of Id without detectable anti-Nase activity. Id expression in such animals could be detected using anti-Id reagents produced in several different species suggesting that it represented true idiotope expression rather than unrelated molecules reactive only with the anti-Id reagent used for initial treatment. Isolation of the nonantigen-binding Id-bearing molecules (Id') showed them to be immunoglobulins bearing the same idiotopes as do anti-Nase antibodies. However, quantitative comparisons of Id levels vs. amount of Id or Id'-bearing immunoglobulin suggested that the nonantigen-binding immunoglobulins bore fewer idiotopes per molecule than did anti-Nase antibodies. Evidence was also obtained for the production of some nonantigen-binding Id-bearing molecules during the normal immune response Nase. These findings are therefore consistent with the existence of a network of Id-anti-Id interactions in the immune response to Nase.

Immunoglobulin secretion by mouse X human hybridomas: an approach for the production of anti-idiotype reagents useful in monitoring patients with B cell lymphoma.

Tumor cells were obtained from a patient with nodular lymphoma, a monoclonal B cell malignancy. These non-Ig-secreting lymphoma cells were hybridized to mouse myeloma cells. Hybridomas secreting human Ig were obtained in high frequency. One clone, which was a stable producer of human heavy and light chains, but which had lost production of mouse light chains, was chosen for study. It secreted a human IgM pentamer. The Ig produced by this clone was purified and used as an immunogen for the production of anti-idiotype antibodies. These antibodies recognized the specific cell surface Ig of the lymphoma cells and have been used to detect idiotype-bearing cells in the blood of the original patient, even at times when the disease was in clinical remission. Moreover, free idiotype could be detected in the patient's serum. Both the levels of Id+ cells and free idiotype correlated with disease activity, rising in relapse and falling in remission.

The degenerative effect on rabbit implantation sites by indomethacin. I. Timing of indomethacin action, possible effect on uterine proteins and the effect of replacement doses of PGF 2α

To determine the effective time of indomethacin (Id) action in disrupting early pregnancy, groups of rabbits were treated at various stages after mating with Id and/or replacement doses of PGF 2α. Effect of Id on the secretion of uterine proteins was also investigated. The highest rate of embryonic death occurred when Id was injected twice daily during days 5–7 of pregnancy, and days 5–6 appear to be the most critical. Persisting levels of Id during this critical stage is required to induce the antifertility effect. The results also indicate that the adverse effect of Id is not mediated through an effect on uterine proteins, and is mainly due to the inhibition of PG's synthesis. PG's are apparently required for normal implantation and early development.

The Lambeth technitray.

Antibody response to the phosphocholine (PC) epitope on Streptococcus pneumoniae R36a (Pn), a T-independent Ag type 2, was studied in H-2 congenic mouse strains. The PC-specific antibody plaque-forming cells (PFC) were enumerated in the spleen at various intervals after the primary Pn injection, and the proportion of PFC that produced antibody expressing the AB1-2 idiotope (Id) was determined by using the corresponding monoclonal anti-Id. AB1-2 is a cross-reactive Id, detectable on germline-encoded PC antibody of the T15 family, and on most, but not all, somatic variants of that antibody. The specific PFC responses in BALB/c (H-2d) and BALB.B (H-2b) strains were of comparable magnitude and most, if not all, PFC were ABl-1 Id-positive (AB1-2+). This was not the case in the responses of the B10D2 (H-2d) vs C57BL/10 (H-2b) strains and the D1.C (H-2d) vs D1.LP (H-2b) strains (on DBA/1 background). In each of these pairs, the H-2d mice were high responders, and the response was dominated by AB1-2 Id (greater than or equal to 80% AB1-2+ PFC at the peak, on day 5). The H-2b mice were low responders, and only a minor proportion of PFC (less than or equal to 30%) were AB1-2+; an increase of AB1-2+ was seen later in the response (d.10). The results of PFC assays were confirmed by measuring the PC-binding antibody and AB1-2 Id in the sera of D1.C and D1.LP mice immunized repeatedly with Pn. Moreover, D1.LP mice that had very low levels of AB1-2 Id had higher serum levels of antibody expressing two other T15 Id, B36-82, and B24-44. The B36-82 and B24-44 Id have been previously found on somatic variants of PC antibody expressed independently of the Ab1-2 Id. The concentrations of these two Id in D1.LP mice after repeated immunization approached those in D1.C. These results indicate that 1) the H-2 allelism may have a significant effect on TID antibody response in mice of a certain genetic background, but not in the BALB/c; and 2) the idiotypic repertoire of the response may be influenced by H-2 at the level of clonal variants of PC-reactive cells.