Lymphotoxin-alpha is an important autocrine factor for CD40 + interleukin-4-mediated B-cell activation in normal and atopic donors. 1998

M Worm, and K Ebermayer, and B Henz
Department of Dermatology, Charité-Virchow Klinikum, Humboldt Universität, Berlin, Germany.

Stimulation of human B cells with anti-CD40 + interleukin-4 (IL-4) results not only in proliferation and immunoglobulin E (IgE)-production, but also increased production of the cytokine lymphotoxin-alpha (LT-alpha) (formerly also known as tumour necrosis factor-beta (TNF-beta)). Here, we studied the role of LT-alpha (TNF-beta) in B cells following stimulation with anti-CD40 + IL-4 from normal versus atopic donors. Anti-CD40 + IL-4 stimulation of peripheral blood mononuclear cells (PBMC) from atopic donors resulted in enhanced production of soluble LT-alpha (TNF-beta) and increased membrane LT-alpha (TNF-beta) expression on the B cells compared with normal donors. Functional evaluation of LT-alpha (TNF-beta) in CD40 + IL-4-stimulated B cells shows that recombinant LT-alpha (TNF-beta) induces proliferation of B cells and enhances CD40 + IL-4-mediated B-cell proliferation and IgE synthesis in both normal and atopic donors in a dose-dependent manner. These findings were supported by semiquantitative analysis of epsilon-germline transcripts using reverse transcription-polymerase chain reaction (RT-PCR) showing increased epsilon-germline transcription in the presence of LT-alpha. Furthermore, addition of anti-LT-alpha (anti-TNF-beta) to CD40 + IL-4-stimulated B cells partially inhibited proliferation and IgE synthesis in a dose-dependent manner indicating a role of endogenous LT-alpha (TNF-beta) production by B cells during continued CD40 + IL-4 stimulation. These data suggest that LT-alpha (TNF-beta) plays a potentially significant role during B-cell proliferation and IgE synthesis. Moreover, LT-alpha (TNF-beta) production seems to be differentially regulated in B cells from normal and atopic donors.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D007139 Immunoglobulin epsilon-Chains The class of heavy chains found in IMMUNOGLOBULIN E. They have a molecular weight of approximately 72 kDa and they contain about 550 amino acid residues arranged in five domains and about three times more carbohydrate than the heavy chains of IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; and IMMUNOGLOBULIN G. Ig epsilon Chains,Immunoglobulins, epsilon-Chain,Immunoglobulin epsilon-Chain,epsilon-Chain Immunoglobulins,epsilon-Immunoglobulin Heavy Chain,epsilon-Immunoglobulin Heavy Chains,Chains, Ig epsilon,Heavy Chain, epsilon-Immunoglobulin,Heavy Chains, epsilon-Immunoglobulin,Immunoglobulin epsilon Chain,Immunoglobulin epsilon Chains,Immunoglobulins, epsilon Chain,epsilon Chain Immunoglobulins,epsilon Chains, Ig,epsilon Immunoglobulin Heavy Chain,epsilon Immunoglobulin Heavy Chains,epsilon-Chain, Immunoglobulin,epsilon-Chains, Immunoglobulin
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008233 Lymphotoxin-alpha A tumor necrosis factor family member that is released by activated LYMPHOCYTES. Soluble lymphotoxin is specific for TUMOR NECROSIS FACTOR RECEPTOR TYPE I; TUMOR NECROSIS FACTOR RECEPTOR TYPE II; and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14. Lymphotoxin-alpha can form a membrane-bound heterodimer with LYMPHOTOXIN-BETA that has specificity for the LYMPHOTOXIN BETA RECEPTOR. TNF Superfamily, Member 1,TNF-beta,Tumor Necrosis Factor Ligand Superfamily Member 1,Tumor Necrosis Factor-beta,Lymphotoxin,Lymphotoxin-alpha3,Soluble Lymphotoxin-alpha,alpha-Lymphotoxin,Lymphotoxin alpha,Lymphotoxin alpha3,Lymphotoxin-alpha, Soluble,Soluble Lymphotoxin alpha,Tumor Necrosis Factor beta,alpha Lymphotoxin
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response

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