Idiotype-specific T lymphocytes responsible for the selection of somatic variants of a B cell hybrid.
A B cell hybrid (2C3E1), which when cultivated in vitro stably expresses a serologically defined private idiotype on the cell surface, undergoes a somatic variation which culminates in the generation of idiotype-negative variants when propagated as a tumor in syngeneic BALB/c mice. Lyt-1+ and Lyt-2- BALB/c T cells derived from appropriately primed spleen cells when co-cultured with 2C3E1 tumor cells in vitro are responsible for the generation or selection of the idiotype-negative tumor variants. The idiotype-specific effector T cells responsible for the variant production in vitro and in vivo are triggered either by viable or irradiated 2C3E1 tumor cells, but not by soluble idiotype-positive monoclonal antibody secreted by the tumor. The idiotype-positive antibody did stimulate the production of the effector T cells when the soluble protein was covalently linked to the plasma membrane of BALB/c spleen cells, but not when the idiotype-positive protein was presented on allogeneic C57BL/6 spleen cells. A single exposure of spleen cells to 2C3E1 cells in vivo was sufficient to prime the idiotype-specific T cells, but the frequency and reproducibility of variant selection increased when the in vivo primed effector T cells were restimulated by irradiated 2C3E1 cells in vitro prior to co-cultivation with the wild-type 2C3E1 cells. The initial variant B cell lines could be segregated into several different phenotypes. However, after extensive cultivation either in vitro or after repeated transfer in vivo, all of the variant cell lines acquired a single stable phenotype that was characterized by the loss of both the surface and secreted idiotype marker and antigen-binding activity associated with the wild-type 2C3E1 cells.
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006822:Hybrid Cells / Q000276:immunology; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010795:Phthalic Acids / Q000276:immunology; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000950:Antigens, Ly; D007130:Immunoglobulin Idiotypes; D010795:Phthalic Acids; C032279:phthalic acid