Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function

Abstract

The possibility was investigated that Ir genes regulate the function of cells other than T or B cells in the primary IgM responses to the synthetic antigens trinitrophenylated poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [TNP-(T,G)-A--L]and trinitrophenylated poly-,-(His,Glu)-poly-D, L-Ala--poly-L-Lys [TNP-(H,G)-A--L]. The primary responses of (B10 × B10.A)F(1) spleen cells to both antigens were abrogated by Sephadex G-10 passage, and restored by the addition of spleen adherent cells. The cell type in the spleen adherent cell population active in reconstituting the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L was a non-T, non-B, radiation-resistant, glass-adherent spleen cell. The responses of Sephadex G-10-passed (responder x nonresponder)F(1) spleen cells to TNP-(T,G)-A--L or TNP-(H,G)-A--L were reconstituted by spleen adherent cells from only responder strains. Spleen adherent cells from F(1) mice reconstituted the responses to both antigens. Spleen adherent cells from each of the strains tested reconstituted the non- Ir gene-controlled response to a third antigen, TNP-keyhole limpet hemocyanin. The inability of spleen adherent cells from nonresponder strains to reconstitute the responses to either TNP-(T,G)-A--L or TNP-(H,G)-A--L was not a result of active suppression induced by the presence of nonresponder adherent cells, since a mixture of responder and nonresponder spleen adherent cells reconstituted the responses to both antigens. The use of spleen adherent cells from recombinant strains demonstrated that the autosomal dominant genes controlling the ability of spleen adherent cells to function as accessory cells in the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L are located in the K or I-A regions of the responder H-2 complex, the same region(s) of H-2 as the Ir genes controlling overall in vitro and in vivo responsiveness to these antigens.

The involvement of suppressor T cells in Ir gene regulation of secondary antibody responses of primed (responder X nonresponder)F1 mice to macrophage-bound L-glutamic acid60-L-alanine30-L-tyrosine.

“…Several studies have shown that nonresponder M~bearing GAT stimulate in vitro primary PFC responses by R or (R × NR)F1 spleen cells (3,4,15). These data differ from those obtained in studies on secondary GAT responses of (R × NR)Ft spleen cells (15) and experiments by others in both the mouse and guinea pig showing the inability of NR-derived antigen-bearing Mq~ to trigger T-cell responses to Ircontrolled antigens (20)(21)(22)(23). One possible explanation for these conflicting data is that NR-Mch pulsed with GAT under nonphysiologic conditions in vitro might artifactually be able to stimulate primary GAT responses, in comparison to NR-M~ bearing GAT acquired in vivo under more physiologic conditions (24).…”

The role of H-2-linked genes in helper T-cell function. VI. Expression of Ir genes by helper T cells.

“…There are a number of possible explanations for the expression of lr genes in helper T cells. Many experiments from this (7,(9)(10)(11) and other (8,15,16) laboratories have shown that/r-genes are expressed in B cells and Mth in a manner consistent with the idea that these genes control the recognition of B-cell-or Mth-bound antigen by T cells. By analogy, it may be, as suggested by Zinkernagel et al (17) and von Boehmer et al (5), that/r-genes, expressed in helper T cells, control the recognition of helper T-cell-bound antigen by a second T cell whose activity is required for the response of the helper T cell.…”

Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGu)-poly(DLAla)--poly(LLys). I. Expression of the genetic defect at two phases of the immune process.

“…(c) When allogeneic combinations were tested, such as of C3H/DiSneducated ceils into C3H.SW recipients (Table IV), or when B 10-educated cells were transferred into B10.A recipients (Table V) (Tables IV and V). We, therefore, suggest that these nonresponder recipients bear a defect in another cell population that is needed for the cooperation with the educated T cells to elicit DTH responses to (T,G)-A--L. A different site for the genetic defect in these strains has been suggested from data of in vitro studies on the cellular basis of humoral immune responses to trinitrophenyl-or dinitrophenyl-coupled (T,G)-A--L. It was suggested that the defect is expressed on the antigen-presenting cell (9,10). However, the results described in this communication agree with data that indicate that the genetic defect in the antibody response of H-2 k and H-2 a mice is not on the level of the helper T cells but in B cells or at a step of T-B-cell interactions (7,8,24).…”