CD40 ligation induces lymphotoxin alpha gene expression in human B cells.
CD40 plays an important role in T cell mediated B cell proliferation and isotype switching. The cytokines tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha are expressed by B cells, and are known to play a role in B cell activation. We have studied TNF-alpha and LT-alpha expression in human tonsillar B cells following stimulation with anti-CD40 mAb. Anti-CD40 induced weak TNF-alpha mRNA expression but strong LT-alpha mRNA expression and had little effect on the constitutive expression of LT-beta mRNA in B cells. Induction of TNF-alpha mRNA was inhibited by actinomycin D suggesting that CD40 ligation results in transcriptional activation of the TNF-alpha and LT-alpha genes. Anti-CD40 caused minimal increase in the expression of TNF-alpha on the B cell membrane and no detectable secretion of TNF-alpha. Anti-CD40 as well as soluble CD40 ligand caused sustained induction of LT-alpha on the membrane of the B cells lasting up to 120 h but induced no detectable secretion of LT-alpha. IL-4, a cytokine known to synergize with anti-CD40 in inducing B cell proliferation and isotype switching, augmented the induction of LT-alpha mRNA and of mLT-alpha expression by anti-CD40. These results indicate that CD40 ligation vigorously induces expression of membrane LT-alpha in B cells and that membrane LT-alpha may play a role in CD40 mediated B cell activation.
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Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115.
Geha
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D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D019013:CD40 Antigens; D023201:CD40 Ligand; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D053308:Lymphotoxin-beta; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D014066:Palatine Tonsil / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; C505886:LTB protein, human; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D015847:Interleukin-4