Mutant EL-4 thymoma cells polyclonally activate murine and human B cells via direct cell interaction.
In this report we show that three mutagenized sublines of (murine) EL-4 thymoma cells can constitutively activate human and/or murine B cells via an MHC-nonrestricted cell-cell interaction. The activation signal is not by itself mitogenic but renders B cells capable of proliferating in response to interleukin 2 (IL 2). In addition, one of the mutant EL-4 sublines can constitutively respond by release of IL 2 in the presence of IL 1-containing macrophage (P388D1) supernatant. The exact relationships between these functional properties of the mutant EL-4 thymoma cells and those associated with activated normal T helper-cells remain to be established. However, the EL-4 cells provide a unique system to study in parallel murine and human B cell responses. In particular, the following observations were made during the present study. First, anti-Ig antibodies (anti-Ig) were required for B cell activation in conjunction with two EL-4 sublines acting only on murine B cells, whereas with a third subline acting on both murine and human B cells, anti-Ig was not required. Anti-Ig by itself did not lead to significant B cell activation in the absence of mutant EL-4 (or normal T) cells. Second, the growth factor-stimulated proliferation of EL-4-activated B cells, following separation of the B cells from the EL-4 cells, lasted only 2 days. These results, thus, indicate that the requirement for a surface Ig-mediated B cell activation signal depends on the quality/intensity of a direct T cell signal and that cell-cell interactions may exert a more stringent control over the growth factor responsiveness of B cells as compared with T cells.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology*; D002460:Cell Line; D003208:Concanavalin A / Q000502:physiology; D006462:Hemolytic Plaque Technique; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000235:genetics / Q000276:immunology*; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D007376:Interleukin-2; D008222:Lymphokines; C021649:concanavalin A-induced helper factors; D003208:Concanavalin A