Thymus and Antigen‐Reactive Cells

334

131

Antigen-binding receptors on T lymphocytes and IgG antibodies with the same antigen-binding specificity as the T-cell receptors display shared or identical idiotypes. This was shown using a system where adult F1 hybrid rats between two inbred strains were inoculated with T lymphocytes from one parental strain. Such F1 hybrid rats produce antibodies directed against idiotypic determinants present on IgG alloantibodies, produced in the T donor genotype strain and with specificity for the alloantigens of the other parental strain. The idiotypic nature of the F1 antialloantibody serum against the parental alloantibodies was demonstrated both by indirect hemagglutination tests or by gel diffusion using alloantisera with different specificity as targets. Furthermore, the F1 anti-T-lymphocyte sera could be shown to contain antibodies against idiotypic parental T lymphocytes as well. This was shown by the capacity of the antisera, in the presence of complement, to wipe out the relevant parental T-cell reactivity against the other parental strain (as measured in MLC or GVH) whilst leaving the T-lymphocyte reactivity against a third, unrelated allogeneic strain intact. These findings demonstrate that F1 hybrid rats inoculated with parental T lymphocytes make anti-idiotypic antibodies directed against both the T cell receptors and IgG alloantibodies of that parental strain with specificity for alloantigens of the other parental strain. In order to prove identity between the anti-idiotypic antibodies against the B and T-cell antigen-binding molecules the following experiments were carried out; highly purified IgG from relevant alloantibody-containing serum in immunosorbent from could be shown to selectively remove both anti-idiotypic activities from the F1 antiserum. Further more, parental normal T lymphocytes could be shown capable of removing from the anti-idiotypic antisera all those antibodies that would cause agglutination of the relevant alloantibody-coated erythrocytes in the indirect agglutination assay. We would thus conclude that T and B lymphocytes reactive against a given antigenic determinant use receptors with antigen-binding areas coded for by the same variable gene subset(s).

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens.

Binz¹,

Wigzell²

1975

334

131

“…The number of plaque-forming cells (PFC) in the draining lymph nodes and the serum antibody levels were measured [10][11]18, and 30-33 days after DNP-GPA immunization. In addition, the avidity of antibody secreted by PFC was measured by a hapten-inhibition technique which allows the enumeration of PFC producing antibody of any given avidity (14).…”

mentioning

confidence: 99%

Hapten-Specific Tolerance

Davie

Paul

Katz

et al. 1972

The treatment of guinea pigs with 2,4-dinitrophenyl (DNP) t derivatives of the copolymer of D-glutamic acid and D-lysine (D-GL) induces a state of specific immunologic tolerance in the recipient (1). The type of tolerance induced is unusual in that it is DNP specific. That is, challenge of such guinea pigs with a DNP conjugate of ovalbumin (DNP-OVA) elicits anti-DNP responses markedly smaller than those of animals which have not been pretreated with DNP-B-GL. The degree of depression in responsiveness is related to the dose of tolerogen, to the mode of immunization with DNP-OVA, and to the interval between the two events. A similar type of haptenspecific tolerance, in mice, has recently been described by both Hraba et al. (2) and by Golan and Borel (3).The tolerant state, in this model, appears to be largely expressed in the precursors of antibody-secreting cells. The evidence for this view is the following:(a) The number of DNP-specific antigen-binding lymphocytes in the lymph nodes of tolerized animals is markedly reduced (1). These antigen-binding lymphocytes are members of the bone marrow-derived (B) lymphocyte pool and include the precursors of antibody-secreting cells (4).(b) The tolerance is hapten specific (1). Thymus-derived (T) lymphocytes acting as "helpers" in the activation of precursor cells are almost exclusively carrier or conjugate specific (5, 6); on the other hand, hapten-specific precursors of antibodysecreting cells are relatively common (4, 7). Hapten-specific tolerance thus implies precursor cell tolerance.(c) Even when an excess of helper cells are provided through an immunization with carrier after tolerance induction with DNP-D-GL but before challenge with DNPcarrier conjugate, the subsequent anti-DNP response is markedly diminished (1). Thus, in a situation in which helper T cells are not limiting, the hapten-specific tolerance is easily demonstrable, again implying a defect in the population of precursors of antibody-secreting cells.

“…Recent studies by Davie and Paul (51,52) presented direct evidence that antibody maturation results from the continued proliferation of higher affinity cells after an immunization, while the number of cells with lower affinity falls rapidly. However, recent advances in cellular immunology argue that selection by antigen is not by itself enough to stimulate antibody-forming cell presursors, and that "helper" T cells are necessary for maximal stimulation of B cells (53)(54)(55). Mediators driving this cellular interaction have recently been reported by several authors (56)(57)(58)(59)(60)(61).…”

Section: Discussionmentioning

confidence: 99%

Dual Regulatory Role of the Thymus in the Maturation of Immune Response in the Rabbit

Taniguchi

Tada

1974

Rabbits thymectomized in early adulthood produced more antihapten antibody than sham-thymectomized controls after hyperimmunization with 2,4-dinitrophenyl bovine gamma globulin (DNP-BGG). The average associated constant of anti-DNP antibody produced by thymectomized animals was more than 10 times higher than that of the controls. Similar effects were obtained by extensive treatment of rabbits with antithymocyte serum (ATS) before and during the immunization with DNP-BGG. The results indicated that relative diminution of thymus-derived lymphocytes (T cells) resulted in a stimulation of antibody-forming cells with a higher affinity. On the other hand, preimmunization of rabbits with different doses of BGG caused either enhancement or suppression of the hapten-specific antibody response, depending on the priming dose of BGG. The suppressed antibody response was always associated with a marked decrease in the antibody affinity. If rabbits were partially tolerized with a large dose of soluble BGG, some of the animals produced little antibody against hapten (DNP) coupled to this carrier, and the affinity of produced antibody was low. However, other rabbits tolerized with BGG produced large amounts of anti-DNP antibody upon hyperimmunization with DNP-BGG, whose affinity was only slightly lower than that of the control. These results can be harmonized if it is assumed that the thymus plays an important role in the maturation of the immune response. It is postulated that T cells, in numbers ordinarily available, would first assist in the proliferation of antihapten antibody-forming cell precursors already selected by antigen, thus accounting for the rapid increase of antibody affinity in the early stage of immunization. However, after a larger number of carrier-specific T cells are made in response to continued immunization, these would suppress antibody-forming cells. The suppression would be greater for cells with higher affinity for antigen, resulting in a decrease in antibody affinity. This postulate explains preferential stimulation and suppression of cells having higher affinity receptors under circumstances in which T cell are relatively depleted or overstimulated, and further permits an explanation for the decrease of antibody affinity after long-term immunization.