title: Cognate interactions between helper T cells and B cells. III. Contact-dependent, lymphokine-independent induction of B cell cycle entry by activated helper T cells.
abstract: An Ag-specific, IL-2-dependent Th clone induced the growth of B cells in a class II-restricted, Ag-specific, IL-2-dependent manner. The formation of stable Th-3.1-B cell conjugates was restricted by Ag and class II MHC. After activation of Th-3.1 by insolubilized anti-T3 (Th-3.1T3), Th-3.1T3 induced the growth of B cells in a class II unrestricted, Ag nonspecific manner. The formation of stable conjugates between Th-3.1T3 and B cells was also class II unrestricted and Ag nonspecific. Although the interaction of Th-3.1T3 and B cells was class II unrestricted, the interaction was inhibited by the combination of anti-IA and anti-IE mAb. This suggested that monomorphic domains of class II MHC molecules were involved in Th-3.1T3-B cell interaction. Fixed Th-3.1T3 but not fixed resting Th-3.1 induced B cell cycle entry, as measured by an increase in B cell RNA synthesis. Trypsin-treatment of Th-3.1T3 before fixation reduced their ability to activate B cells, indicating that cell surface proteins on Th-3.1T3 were required for enhanced B cell RNA synthesis. Anti-IL-4, anti-IL-2R, or anti-IFN-gamma did not affect the ability of Th-3.1T3 to induce heightened B cell RNA synthesis. Progression into S phase by B cells activated with fixed Th-3.1T3 was supported by the addition of soluble factors. When stimulated with fixed Th-3.1T3, EL4 supernatant (SN) enhanced B cell DNA synthesis. Depletion of IL-4, but not IL-2, from EL4 SN ablated its supportive capabilities. IL-4 alone was completely ineffective in supporting entry into S phase. Therefore, IL-4 and another activity(ies) in EL4 SN were necessary for B cell cycle progression into S phase. Taken together, these data suggest that after Th activation, Th cell surface proteins are expressed that mediate the binding of Th to B cells via recognition of nonpolymorphic domains of class II MHC molecules. Contact of Th-3.1T3 with B cells, not lymphokines, results in the entry of B cells into the cell cycle and heightened B cell lymphokine responsiveness. The addition of exogenous lymphokines supports the progression of Th-3.1T3-activated B cells into S phase.
authors: Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755.
authors: R J
authors: RJ
authors: Noelle
authors: J
authors: J
authors: McCann
authors: L
authors: L
authors: Marshall
authors: W C
authors: WC
authors: Bartlett
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D017252:CD3 Complex; D002450:Cell Communication; D002453:Cell Cycle; D004247:DNA / Q000096:biosynthesis; D000939:Epitopes; D005260:Female; D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology; D007399:Interphase; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000939:Epitopes; D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA