Natural killer cell suppression of IgM production.
The mechanisms by which natural killer (NK) cells regulate B cell function are not well understood. In this paper, the suppressive effects of NK cells on IgM production by lipopolysaccharide (LPS)-stimulated B cells were studied. We found that interleukin (IL)-2-activated NK (NKa) cells, but not unstimulated NK cells, suppressed IgM production by B cells stimulated with LPS. Suppression of antibody production required direct NKa-B cell contact, as demonstrated in cultures utilizing semiporous membranes for cell separation, and was the consequence of a reduction in the number of IgM-producing cells, as determined by enzyme-linked immunospot assays. Suppression could not be accounted for by cytotoxic mechanisms since the NKa cells caused neither cytolysis of 51Cr-labelled B cells or B cell apoptosis. While NKa-B cell contact was necessary for suppression, cell contact alone was not sufficient. Rather, both NKa-B cell contact and NKa production of interferon (IFN)-gamma were necessary. Since only IL-2-activated, but not unstimulated, NK cells suppressed IgM production, we investigated the potential for IL-4, which has been reported to downregulate IL-2-induced NK cell proliferation, to prevent NKa cell suppressive activity. While IL-4 antagonized IL-2-induced NK cell proliferation, it was completely ineffective in antagonizing NKa cell suppression of IgM production. The requirement for IL-2 activation of NK cells for suppression of IgM production suggests that NK cells may be part of a physiologic negative feedback mechanism to downregulate antibody production.
Department of Microbiology, College of Medicine, Houston, Tex. 77030.
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D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D007108:Immune Tolerance / Q000502:physiology*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D007075:Immunoglobulin M; D007376:Interleukin-2; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma