Role of T cells in the B-cell response: glutaraldehyde-fixed T-helper hybridoma cells synergize with the lymphokine IL-4 to induce B-cell activation and proliferation.
Antigen-unselected helper T-cell hybridomas (Th) which activate normal resting B cells to RNA synthesis and proliferation in the presence of concanavalin A (Con A) have been developed. The response is completely Th cell dependent, and not restricted by the haplotype of the B-cell major histocompatibility complex (MHC). Culture supernatants from the Con A-stimulated Th hybridomas contain interleukin-4 (IL-4) and IL-2, but undetectable level of IL-5. The supernatant alone, however, does not induce B-cell activation or proliferation. Although the Con A-mediated Th cell-dependent B-cell response occurs in an MHC-unrestricted manner, the response of resting B cells can be blocked by monoclonal Ia antibody specific for the surface class II molecules of the responding B cell. The response is also blocked by monoclonal antibody to L3T4. Significant activation and proliferation of resting B cells can also be triggered by glutaraldehyde-fixed Th hybridomas and Con A when exogenous IL-4 is added. The stimulation with fixed Th hybridomas plus IL-4 can be inhibited by monoclonal anti-L3T4 or anti-Ia. These results suggest that maximal B-cell activation requires a direct helper T cell-B cell interaction which depends on availability of Ia on the B cell and L3T4 on the T cell, even when Con A overcomes the requirement for MHC-restricted T-cell recognition. We suggest that this signal, in conjunction with T-cell produced lymphokine IL-4, is responsible for the activation and subsequent proliferation of the B cells which occurs following interaction with T cells.
Kubota
E
E
Department of Oral Surgery, Saga Medical School, Japan.
McKenzie
D T
DT
Dutton
R W
RW
Swain
S L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003208:Concanavalin A; D004247:DNA / Q000096:biosynthesis; D005404:Fixatives; D005976:Glutaral; D006825:Hybridomas / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D005404:Fixatives; D007376:Interleukin-2; D003208:Concanavalin A; D015847:Interleukin-4; D004247:DNA; D005976:Glutaral