Cellular and Genetic Control of Antibody Responses

Abstract

The expression of Ir gene function has been analyzed in the in vitro primary anti-hapten response to TNP-(T,G)-A—L. Helper T cells, B cells, and accessory cells of responder H-2^b and nonresponder H-2^a origin were individually assessed for the ability to support PFC responses to TNP-(T,G)-A—L.

For the normal B10.A (H-2^a) nonresponder, it was found that the accessory cell function of the spleen adherent cell (SAC) population was under H-2 linked Ir gene control, since B10 (H-2^b) but not B10.A (H-2^a) SAC were capable of reconstituting responses to TNP-(T,G)-A—L by responder T cells and B cells. In contrast, the function of nonresponder B10.A B cells was not under H-2 linked Ir gene control, since nonresponder B10.A B cells were as effective as responder B10 B cells in responding to TNP-(T,G)-A—L.

The ability of B10.A → (B10 × B10.A)F₁ (B10.A → F₁) chimera spleen cells to respond to TNP-(T,G)-A—L was also investigated. It was demonstrated that B10.A → F₁ spleen cells, which were greater than 95% donor (H-2^a) origin, were nonresponders, i.e., the overall nonresponder phenotype of B10.A cells was not altered by maturation in the chimera environment. In experiments designed to examine the competence of each cell subpopulation of B10.A → F₁ chimera spleen, it was found that nonresponder (H-2^a) B10.A → F₁ T cells provided effective help for the response to TNP-(T,G)-A—L when cooperating with responder B10 (but not nonresponder B10.A) SAC accessory cells; and that nonresponder (H-2^a) B10.A → F₁ B cells were similarly effective in supporting the response to TNP-(T,G)-A—L in the presence of responder accessory cells. Finally, B10, but neither B10.A nor B10.A → F₁, SAC were competent to reconstitute the response of accessory cell-depleted (B10 × B10.A) F₁ spleen cells to TNP-(T,G)-A—L.

Taken together, these results demonstrated that the Ir gene-controlled unresponsiveness of H-2^a nonresponder spleen cells was expressed only at the level of the accessory cell, and not by either T cells or B cells. Thus, H-2^a spleen cells are nonresponders to TNP-(T,G)-A—L, because the only accessory cells normally available for presenting TNP-(T,G)-A—L are nonresponder H-2^a. Whether the defect is intrinsic to nonresponder accessory cells or is due to the functional absence of helper T cells (or B cells) capable of responding to antigen presented by nonresponder accessory cells has not been established.