Relationship Between Antigen and Antibody‐Induced Suppression of Immunity

Self Cite

A critical stage in the induction of antibody responses is the interaction of antigen molecules with the surface receptors of immunocompetent cells. This interaction may result in either immunity, or its opposite, immune tolerance. The differences between the pattern of antigen binding to nonthymus-dependent lymphocytes (B cells) 1 in immunity and tolerance are not fully understood. Recently, attempts were made to study this problem in tissue culture, using dinitrophenylated polymeric flagellin (DNP POL) as antigen (1). The interaction of antigen molecules with cell membranes may be readily studied in dissociated lymphoid cell populations in vitro, where antigen concentrations are relatively uniform and catabolism negligible compared with tile situation in vivo (2). Furthermore, since tile response to DNP POL in vitro does not require the participation of either thymus-dependent lymphocytes (T cells) (1, 3) carrier-reactive cells, or macrophages (4, 5), only the pattern of reaction of DNP POL molecules with B cells determines the ensuing immunological events. It was found that the number of 2,4-dinitrophenyl (DNP) haptenic groups present per monomeric unit of the DNP POL molecule (i.e. the epitope density) dictated its capacity to induce either immunity or tolerance (1). Antigen molecules with few DNP groups immunized, but never induced tolerance, whereas highly conjugated DNP POL induced tolerance, but never immunity (1). Based on these observations, a mechanism of B celt signal discrimination between immunity and tolerance was proposed, based on the number

Section: Discussionmentioning

confidence: 53%

Induction of Immunity and Tolerance in Vitro by Hapten Protein Conjugates

Feldmann

1972

Self Cite

“…Much interest has centered on the importance of epitope density in tolerance induction, a high density of determinants putatively favoring tolerance induction (21). In the case of simple protein antigens, it has been proposed that antigen-antibody complexes may supply the required epitope density (21).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of simple protein antigens, it has been proposed that antigen-antibody complexes may supply the required epitope density (21). This mechanism is unlikely to be relevant in the present model, firstly, since there is no detectable antibody formation with the injection of FGG alone into the nude mouse (unpublished data); secondly, since the amount of antigen injected is relatively large; and thirdly, since the tolerance is established within 24 h, before antibody synthesis would be underway.…”

Section: Discussionmentioning

confidence: 99%

Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

Schrader

1974

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.

“…Since IBF is synthesized by T cells (13) and since IgG is known to participate in the regulation of B-cell responses (15), it is interesting to speculate on whether IBF might interfere with antibody synthesis . In the present communication, we describe the suppressive effect of IBF on the synthesis of antibodies to T-dependent and T-independent antigens in vitro and submit that IBF may be a soluble mediator of suppressor T cells.…”

mentioning

confidence: 99%

Suppression of in vitro antibody synthesis by immunoglobulin-binding factor.

Gisler¹,

Fridman²

1975

119

Alloantigen-activated mouse T cells secrete a factor which binds to the Fc fragment of IgG and blocks complement (C) activation by IgG (immunoglobulin-binding factor, IBF). IBF was found to suppress the direct plaque-forming cell (PFC) response of mouse spleen cell cultures to sheep erythrocytes and to dinitrophenylated aminoethyldextran (T-independent antigen). Purification of IBF by affinity chromatography on IgG-coated Sepharose columns led to an increase of the suppressive capacity with IgG, IgM, or Fab2 from IgG) the factor responsible for inhibiting the PFC response could not be dissociated from that responsible for the inhibitory activity of IBF on C-dependent hemolysis. No effect was seen when cultures were pretreated for 6 h, or when IBF was added at 72 h. These data are compatible with the view that IBF is a soluable mediator of suppressor T cells which may interfere with terminal differentiation of antibody-forming cell precursors.