Genetic control of immune responses in vitro. I. Development of primary and secondary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro

In vivo, the antibody response in mice to the random terpolymer L-glutamic acid⁵⁰-L-alanine³⁰-L-tyrosine¹⁰ (GAT) is controlled by a histocompatibility-linked immune response gene(s). We have studied antibody responses by spleen cells from responder and nonresponder mice to GAT and GAT complexed to methylated bovine serum albumin (GAT-MBSA) in vitro. Cells producing antibodies specific for GAT were enumerated in a modified Jerne plaque assay using GAT coupled to sheep erythrocytes as indicator cells. Soluble GAT stimulated development of IgG GAT-specific plaque-forming cell (PFC) responses in cultures of spleen cells from responder mice, C57Bl/6 (H-2^b), F₁ (C57 x SJL) (H-2^b/s), and A/J (H-2^a). Soluble GAT did not stimulate development of GAT-specific PFC responses in cultures of spleen cells from nonresponder mice, SJL (H-2^s), B10.S (H-2^s), and A.SW (H-2^s). GAT-MBSA stimulated development of IgG GAT-specific PFC responses in cultures of spleen cells from both responder and nonresponder strains of mice. These data correlate precisely with data obtained by measuring the in vivo responses of responder and nonresponder strains of mice to GAT and GAT-MBSA by serological techniques. Therefore, this in vitro system can effectively be used as a model to study the cellular events regulated by histocompatibility-linked immune response genes.