NATURAL-KILLER-CELL SUPPRESSION OF IGM PRODUCTION

The mechanisms by which natural killer (NK) cells regulate B cell func tion are not well understood. In this paper, the suppressive effects o f 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 require d direct NKa-B cell contact, as demonstrated in cultures utilizing sem iporous membranes for cell separation, and was the consequence of a re duction in the number of IgM-producing cells, as determined by enzyme- linked immunospot assays. Suppression could not be accounted for by cy totoxic mechanisms since the NKa cells caused neither cytolysis of Cr- 51-labelled B cells or B cell apoptosis. While NKa-B cell contact was necessary for suppression, cell contact alone was not sufficient. Rath er, both NKa-B cell contact and NKa production of interferon (IFN)-gam ma 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 proli feration, to prevent NKa cell suppressive activity. While IL-4 antagon ized IL-2-induced NK cell proliferation, it was completely ineffective in antagonizing NKa cell suppression of IgM production. The requireme nt for IL-2 activation of NK cells for suppression of IgM production s uggests that NK cells may be part of a physiologic negative feedback m echanism to downregulate antibody production.