Tumor necrosis factor selectively inhibits activation of human B cells by Epstein-Barr virus.
We have investigated the effect of recombinant human tumor necrosis factor-alpha (rTNF-alpha) on human B cell activation and differentiation. Among several T cell-dependent and independent B cell stimulation systems tested (anti-mu, pokeweed mitogen, Epstein-Barr virus), only the activation by Epstein-Barr virus was inhibited by rTNF-alpha. rTNF-alpha inhibited in a dose-dependent manner both the proliferation and differentiation (Ig secretion) of Epstein-Barr virus-stimulated B cells when added at the beginning or within 48 hr of a 6 to 8-day culture period. Maximal suppression (80 to 95%) was found at rTNF-alpha concentrations of 10 to 50 ng/ml. Inhibition of B cell activation required the presence of significant numbers (25%) of plastic adherent macrophages within the B cell population. Suppression was not due to lysis of Epstein-Barr virus-infected B cells by rTNF-alpha-treated macrophages. As shown by double chamber experiments where macrophages and B cells were separated by a 0.45-micron membrane, macrophages elaborated factors in response to rTNF-alpha, which, alone or synergistically with rTNF-alpha, inhibited B cell activation. These factors were different from prostaglandin E2, interferon-alpha, and interleukin 1. We conclude that rTNF-alpha can dramatically modulate certain normal immune responses in vitro.
Janssen
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Department of Medical Microbiology and Immunology, University of Ulm, Federal Republic of Germany.
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D001402:B-Lymphocytes / Q000166:cytology*; D001688:Biological Products / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000502:physiology*; D015846:Monokines; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001688:Biological Products; D007075:Immunoglobulin M; D007136:Immunoglobulins; D015846:Monokines; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha