Suppression of B cell responses by natural killer cells is mediated through direct effects on T cells.
We examined the ability of human natural killer (NK) cells to modulate T cell-dependent mitogen-induced B cell responses. Highly purified NK cells inhibited the polyclonal antibody responses of autologous pokeweed mitogen (PWM)-stimulated unfractionated mononuclear cells in a reverse hemolytic plaque-forming cell (PFC) assay. Investigation of the possible mechanism(s) of the suppressor activity of NK cells revealed that lysis of mitogen-stimulated cells was unlikely. Chromium-51 release cytotoxicity assays of PWM-stimulated mononuclear cells did not demonstrate lysis by NK cells. Additionally, the monoclonal antibody 13.3, which abrogates NK cell cytolysis, did not reverse NK cell-dependent suppression of PFC formation. The putative lytic molecule elaborated by NK cells, NK cytotoxic factor, did not suppress B cell responses, further supporting a nonlytic inhibitory mechanism. That NK cell-derived lymphokines such as IFN-alpha, IFN-gamma, or IL-2 were uninvolved in the down-regulation of B cells was corroborated by the failure of antibodies to these mediators to reverse the suppression. NK cells did not suppress PFC formation when T cells were replaced by supernatants from PWM-stimulated T cells; additionally, NK cells had no effect on the generation of these necessary T cell factors. However, the coculture of T cells with NK cells resulted in the induction of suppressor activity within the T cell population suggesting that this was the mechanism of NK cell-mediated suppression of B cell responses.
Department of Medicine, Georgetown University Medical Center, Washington, D.C. 20007.
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P
Katz
S R
SR
Mitchell
T R
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Cupps
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M
Evans
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G
Whalen
D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000502:physiology*; D008222:Lymphokines / Q000502:physiology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
D008222:Lymphokines; D011043:Pokeweed Mitogens