title: Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells.
abstract: Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-dependent help. Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction, but has also been linked to the induction of B cell apoptosis. To examine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell receptor-MHC interaction through a bacterial superantigen. CD4+ T cell clones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. One subset of T cell clones supported immunoglobulin synthesis, and thus functioned as effective helper cells. B cells interacting with the second subset of T cells did not differentiate into antibody-secreting cells, but underwent apoptosis. Both types of helper cells were able to provide contact help after anti-CD3 stimulation. Induction of apoptosis was a dominant phenomenon; the addition of the superantigen suppressed immunoglobulin production in B cells activated by anti-CD3-stimulated helper T cells, indicating that the T cells delivered an apoptotic signal to the B cell. T cell clones providing effective MHC restrictive B cell help could be distinguished from T cells facilitating B cell apoptosis based on their lymphokine secretion profile. Induction of B cell apoptosis was a feature of T cells with a TH0 lymphokine pattern. Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. TH1-derived cytokines alone could not substitute for apoptosis-inducing T cells.
authors.affiliation: Division of Rheumatology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: W
authors.initials: W
authors.lastname: Zhong
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; D006684:HLA-DR Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma