Hapten-Specific Tolerance

We have described a model of immunological tolerance induced, in adult mice, by a single injection of a moderate dose of a hapten-protein conjugate. The data suggest that the mechanism of this tolerance state is the production of small amounts of high affinity antibody in response to the tolerance-inducing antigen injection. This antibody acts to inhibit the response to a subsequent challenge with antigen in complete Freund's adjuvant by a mechanism comparable to that of passive antibody-medicated immune suppression. It was shown that a small but high affinity. Tolerance was not terminated by transfer of normal syngeneic spleen or peritoneal cells into tolerant animals. Spleen cells from tolerant mice, when transferred into lethally irradiated, syngeneic animals, produced a PFC response which is greater in magnitude and tolerance state had a significant degree of carrier specificity which was shown to be comparable to the carrier specificity of antibody-mediated immune suppression. hus, evidence was presented to show that one mechanism of tolerance in adult animals in the suppressive effect of small amounts of high affinity antibody formed in response to the tolerizing injection of antigen.

Section: Methodscontrasting

confidence: 52%

“…Consequently, B-cell tolerance has been found to be associated with a marked depression in antibody affinity (13,(15)(16)(17)(18) . The tolerant state described in the current work is thus distinctive in that it is associated with an increase in antibody affinity .…”

Section: Discussionmentioning

confidence: 99%

Demonstration of an antibody-mediated tolerance state and its effect on antibody affinity.

Birnbaum¹,

Weksler²,

Siskind³

1975

“…The most effective methods employed have the common feature of treating animals with haptenic determinants on molecules or substances that fail to stimulate T cells, or do so very poorly. Thus, such tolerance has been induced by administration of (a) hapten on nonimmunogenic moieties such as the synthetic copolymers of D-glutamic acid and n-lysine (D-GL), 1 or ~GL in PLL nonresponder guinea pigs (5,6) or inbred mice (7,9), (b)haptenic derivatives of autologousproteins (10)(11)(12)(13)(14), autologous or syngeneic red cells (15), or (c) polysaccharides such as type III pneumococcal polysaccharide (16,17). We suggested earlier that a possible explanation for the ease of tolerance induction with the hapten conjugates of nonimmunogenic copolymers such as D-GL and also for other non-or weakly immunogenic substances may be the lack of the simultaneous occurrence of immunization and tolerance induction when these substances are administered in appropriate conditions (1, 5).…”

Section: (From the Department Of Pathology Harvard Medical School Bmentioning

confidence: 99%

Immunological Tolerance in Bone Marrow-Derived Lymphocytes

Katz

Hamaoka

Benacerraf

1974

Self Cite

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.

“…It also offers a clue to the understanding of more sophisticated roles of T cells in the regulation of antibody response, namely, the selective pressure of T cells on B-cell response with respect to the 'shift' in the class and affinity of produced antibody in the time course of antibody response. Furthermore, the preferential suppression of high affinity antibody formation caused by suppressor T cells is clearly analogous to the feature in the immunological tolerance produced by high doses of antigen (27)(28)(29). In view of the observation made by Gershon and Kondo (30) on the infectiousness of immunological tolerance by T cells, the attribute of suppressor T cells to the induction of immunological tolerance should await further analysis.…”

Section: Suppression Of Relative Avidity Of Pfc For Hapten By Carriermentioning

confidence: 99%

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Takemori

Tada

1974

Our preceding studies indicated that thymus-derived lymphocytes (T cells) primed with a carrier antigen suppressed antibody responses by bone marrowderived lymphocytes (B cells) against a hapten coupled to the homologous carrier, when they were transferred into immunized recipients (1). The degree of suppression in IgM and IgG antibody responses differed depending primarily on the time when suppressor T cells were transferred to the recipients. Thus, it appeared that susceptibility of B cells to the regulatory influence of T cells is inherently different according to the differentiation stages of B cells following antigenic stimulation. The results are in accordance with the widely noted distinction between IgM and IgG antibody responses with respect to their dependency on T cells (2-4).Another important facet observed in the above T-cell-mediated suppression of antibody response is the strict specificity of both T and B cells for the immunizing antigen: to elicit effective suppression T cells must be primed by the carrier on which haptens are coupled. These observations suggest that T cells would specifically influence the emergence and selection processes of B cells by antigen, resulting in the observed preferential suppression of certain populations of antibody-forming cells. It has been generally accepted that antihapten antibodies are heterogeneous with respect to their affinity for hapten, which probably reflects the heterogeneity among B cells (5-8). It has also been noted that the intrinsic affinity of IgM antibodies is usually lower than that of IgG antibodies (9-11). In view of these immunochemical bases, the present experiments were undertaken to study what subpopulations of B cells with regards to the affinity of produced antibody are, in fact, selectively suppressed by the carrier-specific T cells. Materials and MethodsMost essential experimental details have already been described in the preceding paper (1), and only a few points are added here.