title: T cell-dependent activation of B cell proliferation and differentiation by immobilized monoclonal antibodies to CD3.
abstract: The capacity of mAb directed at the CD3 molecular complex (64.1) to induce T cell-dependent B cell proliferation and differentiation was examined. Coculture of B cells with mitomycin C-treated T4 cells (T4 mito) stimulated by immobilized 64.1 resulted in marked B cell proliferation and Ig-secreting cells (ISC) generation in the absence of any additional stimulation. The magnitude of the B cell responses induced by immobilized 64.1-stimulated T4 mito was far greater than that induced by other stimuli, such as Staphylococcus aureus plus factors produced by mitogen-activated T cells, PWM, or soluble 64.1. The induction of maximal B cell responsiveness required direct contact between activated T cells and responding B cells. Of note, immobilized 64.1 also induced B cell proliferation and ISC generation in the presence of mitomycin C-treated T8 cells. By contrast, immobilized 64.1 stimulated T4 or T8 cells that had not been treated with mitomycin C induced very modest ISC generation and suppressed B cell responses supported by T4 mito even in the presence of exogenous IL-2 or factors produced by mitogen-activated T cells. The interactions between T and B cells in these cultures not only induced B cell responses, but also enhanced the production of IL-2 by activated T cells. Increased IL-2 production was facilitated when culture conditions afforded the opportunity for contact between B cells and activated T cells. These results indicate that the establishment of interactions between B cells and anti-CD3-stimulated T4 or T8 cells provides all of the signals necessary for proliferation and differentiation of B cells without other stimuli and also augments the production of lymphokines by the activated T cells. The data emphasize the role of Ag-nonspecific interactions between B cells and T cells in promoting polyclonal responses of both cell types.
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center, Dallas 75235.
authors.forename: S
authors.initials: S
authors.lastname: Hirohata
authors.forename: D F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000921:Antibody-Producing Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D017252:CD3 Complex; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D008937:Mitomycins; D011948:Receptors, Antigen, T-Cell; D016685:Mitomycin